WPT University Place Wednesday Nite at the Lab  Barbara Klein "The Beaver Dam Eye Study"  February 16, 2011 UP555   cc >> Tom Zinnen: Welcome, everyone, to Wednesday Nite at the Lab. I'm Tom Zinnen. I work here at the UW Madison Biotechnology Center and for UW Extension Cooperative Extension, and on behalf of the Wisconsin Alumni Association and Wisconsin Public Television, thanks again for coming to Wednesday Nite at the Lab. We do this every Wednesday night, 50 times a year. Tonight I'm delighted to be able to introduce to you Barbara E.K. Klein who's both a physician and a master of public health. She's a professor in the Department of Ophthalmology and Visual Sciences and is affiliated with the Department of Population Health Sciences here at the University of Wisconsin Madison. She is also the co-director of the Beaver Dam Eye Study which will be the subject of her talk tonight. This study collects information on the prevalence and incidence of age-related cataract, macular degeneration and diabetic retinopathy, which are all common eye diseases in an aging population. The study also has examined other aging issues such as overall health, quality of life and environmental and medicinal exposures. Please join me in welcoming Dr. Klein to Wednesday Nite at the Lab. 

[APPLAUSE] >> Barbara Klein: Thank you very much for coming out this evening. I know it wasn't fun walking through the ice and slush. I'll get started and I think there will be plenty of time at the end for questions. So here it goes. This is the banner story in the Daily Citizen, the Beaver Dam Daily Citizen, in 1987. After about two years of writing and rewriting grant proposals to the NIH, the Beaver Dam Eye Study was funded, and the newspaper's been a very wonderful supporter of this study. Let's see, the reason that the Beaver Dam Eye Study was conceived and designed was because at the time, 1985 or so, there was very, very little information on the common chronic eye conditions, not esoteric things but things all of us will likely face with regard to how common they were, what was the incidence or new development after so many years of life and then what were risk factors in particular for these common conditions. In particular, we looked at the functional end point, which is visual impairment and severe visual impairment or legal blindness, but then we looked at the causes which are cataracts, glaucoma, age-related degeneration or macular degeneration, and, as was pointed out by Tom also, diabetic retinopathy. We got a lot of information about other things as well, some of which I'll share with you this evening. Retinal vein occlusion as it turned out was more common than we had anticipated, and this is also a big problem. 

Well you may be quite familiar with where Beaver Dam is. It's about 39 miles northeast of Madison, not far from Milwaukee as well. It's about equal distance between the two. We painted this in Badger red because of the Rose Bowl. So why Beaver Dam? I've been asked this question innumerable times. We chose Beaver Dam because it was very representative of other small communities throughout the Midwest. It had the appropriate size population for adequate sample sizes to test the hypotheses we were interested in. Beaver Dam had a high participation rate in an earlier study that we had done. And the community leaders from all walks of life as well as the physicians and eye care providers, including eye doctors and optometrists which at the time was unusual, all cooperated and were supportive. Also very important was that it was close to Madison, and if something happened at the field center in Beaver Dam and I was at my office in the WARF building, I could get there within an hour. 

So this is a picture of the gazebo in Swan Park, and in times past there used to be springs, excuse me.  People would come to take the waters in Beaver Dam and they'd be dealt this Swan Park gazebo. Pardon me for a minute.  Sorry. Well, a very important part of the project was getting an accurate census. This is one of our census takers in action. [LAUGHTER] The census was done between 1987 and 1988 to determine the actual number of people in the target age range as well as to ascertain or confirm their current addresses. We had estimates from the previous census, the national census, but this was many years after and we had to update it. We also wanted to introduce ourselves to the community, in particular each household where we would be recruiting study participants. We also collected some very basic information about vision and self-reported eye conditions. 

By doing this, we identified 5,924 people 43 to 84 years of age. That was our target range. Each participant received an invitation to the study followed up by a call and then a scheduling of appointments. We did a study evaluation which took about two and a half hours for each participant. Then we collated all the information, and those who wanted the information back received it as well as their healthcare providers, if they chose to do that. And then, of course, the big part is the analysis of the wealth of information that came in after that. Took us about two and a half years the first time through with the arduous recruitment back and forth, but the participation rate has been tremendous in Beaver Dam. It's been a wonderful community to work in, and we're still working there. And I'll tell you a little bit more about that in a moment. I'm sort of cutting to the chase here, and this is a summary of the prevalence. 

Prevalence is a cross-section of the population at the time of the first exam. So this is prevalence of visual impairment. Visual impairment means visual acuity of 20/40 or worse after an in depth refraction and using that optimal correction. So we call this the best corrected visual acuity. And you can see from the slide that visual impairment is very uncommon in the youngest age group, the 43- to 54-year-olds, and it stays very low until that last decade or so when it increases to about 20% of people. Excuse me again.  This plots the data for legal blindness which is about 2200 or worse in the better eye.  You can see that woman are disproportionately disadvantaged compared to men. Once again, you notice that the scale is different but, again, it's that big increase after age 65. Oops, sorry. 

I'll go now through the individual eye conditions. So the first one would be cataract. A picture of me at an earlier stage in my career. [LAUGHTER] In front of a slit lamp, which we use to examine for cataract, and right next to it is a camera that we use to take photos of the lens. I'm also pointing out to one of the study participants where we're looking at when I look at the lens of the eye. There are three kinds of age-related cataract: nuclear cataract, cortical cataract, and posterior subcapsular cataract. These photographs are taken after the pupil is dilated with dilating eye drops, and a light beam comes in at 45 degrees from where the camera is angled so that you get a sort of a cross-section and you get the impression of sort of layers or like layers of an onion. And on your left is a relatively young lens, very little nuclear sclerosis. And on your right is someone where the nucleus, which is the center part, is dense or less clear. That's a nuclear cataract. 

This photograph was taken, or this set, through a dilated pupil but with a different sort of camera. Here, it's called a retroillumination camera, a bright light is shown into the eye, and the reflected light from the retina gives it that orange appearance. On your left is a clear lens, no cataract. On your right is cortical cataract. Excuse me again.  I'm so sorry. This is another form. This is the posterior subcapsular cataract. The one on your left again is clear. This opacity is in the back part of the lens, and it tends to be very visually disabling. 

Why is preventing cataract important? Cataract is the leading cause of blindness worldwide. It's more common as the cause of blindness than a variety of parasitic infections that used to be quoted as being the most important. It's also the leading cause of loss of vision in the US. It's responsible for about 60% of all Medicare costs related to vision. So it's a big problem. Cataract surgery which is relatively easy to come by in this country can be complicated, there are always complications for surgery or at least you have to anticipate they could happen, it can be uncomfortable, it's expensive and it may not be able for those with limited or no healthcare coverage. I think this is going to be a bigger and bigger problem. It's also not widely available in some Third World countries. This again is a summary of the data from the first Beaver Dam study. And you can see the tall bars are the prevalence of cataract, and you can see once again that inexorable increase with increasing age but by the time we got there, there were a number of people who had already had some cataract surgery, usually with implants in place. 

Rises to be about, cataract is about 80% of the population 75 or older. When I group together the three kinds of cataract you can see, again, the increase with increasing age because they are all age related, and once again you can see that women are disproportionately affected. This is just a summary of the prevalence of the three different kinds. So you can see that 17% of the people had nuclear cataract, not rare. Cortical, about 16%. Posterior subcapsular, the most visually disabling, about 6%, and cataract surgery had been done in about 3.6% of people. Well, what are the causes of this? Are there environmental causes to these problems? It looks like smoking increases the risk of cataract quite significantly, most significantly for nuclear cataract. I would point out that for the others it's not statistically significant all the time. And this may be a sample size issue. But that 1.09 means that smokers who smoke 10 pack-years will have a 9% increase in risk. 

But most smokers or many smokers have smoked more than 10 pack-years in their lives. So you can see it becomes quite a significant cause for increase in nuclear cataract which is the most common cause of cataract surgery. A little bit less and not statistically significant for cortical and a smaller effect on posterior subcapsular cataract. I'm going the wrong way. Past heavy drinking it appears is also associated with cataract. And you can see it appears to increase the risk of all three kinds of cataract. I have a colleague in Rotterdam doing the Rotterdam Eye Study that was patterned after Beaver Dam, and when I told him we consider heavy drinking to be four or more drinks per day on a regular basis. And he said, that's not heavy drinking, everybody drinks that much. [LAUGHTER] But that's not true in Beaver Dam. And so we have relatively few heavy drinkers, but they are apparently at increased risk. 

Well there are other factors that are environmental factors that are associated with cataract. There's evidence that UVB is associated with cortical cataract in men. UVB is the common UV radiation that comes in with blue light when you're outdoors, and we found an increased risk in Beaver Dam and also there have been other studies to corroborate this. And there may be an association with CAT scans to the head but that's less clear. So what have we learned about cataract from the Beaver Dam Eye Study or from the prevalence data at any rate? We found that more than 80% of people who were over the age of 75 had cataracts, that's pretty prevalent. Women were more likely to be affected than men. Smoking, heavy drinking were associated with nuclear cataract. UVB exposure, diabetes, past heavy drinking were associated with cortical cataract. Diabetes, steroid use, past heavy drinking were associated with posterior subcapsular cataract. So they seem to have slight differences in their risk factors. 

Do we know anything about protection? Of course the idea is to find things that you can intervene on to protect people from getting this. Well, the data about multivitamins is tenuous. We found a significant effect but not strong for cortical cataract. Some studies find it, some don't. Something that we found five years ago and reported was statistically significant protective effect of statin drugs for cataract, in particular for nuclear cataract. We have yet to see this replicated, although the Blue Mountains Eye Study, sister study right now, the Blue Mountains of Australia right outside of Sydney, found a very similar protective rate but it wasn't statistically significant. So we have yet to see. It hasn't been tested in a trial. I'm going to move along to another common condition in Beaver Dam, age-related macular degeneration. And you all may know something about this. 

There really was very little information about this disease when we started. So we were interested in both the incidence and progression when evidence of some of the disease was already there. Its risk factors and then we have some information about treatments to prevent or restore vision in the late stage. So this is one of our field examiners using this camera. This is a particular camera designed to take photographs of the retina. It's a fundus camera. Not easy to use for the examiner, not so easy for the patient either, the participant either. So this montage shows you just a quick glimpse of fundus, that is retinal photos of eyes that have different degrees of this lesion, or this condition. On the top we see early age-related macular degeneration, and you see that there are a lot of yellow spots there. The blood vessels are normal, the optic nerve looks good, but those yellow spots, if you want, are called drusen, and they're excrescences in the deep layers of the retina, and this person would likely have no symptoms at all. 

On the bottom you see two pictures of late age-related macular degeneration. The one on your left is called geographic atrophy, the bottom is cut off, and essentially the retina is missing in what appears to be a geographically defined area. And of course you can't see in that area. The other one is called neovascular or wet AMD and that red stuff is blood. There's been new growth of vessels from the choroid, a vascular layer under the retina, and this new vessel membrane is very friable and fragile, and it often breaks, bleeds and people can go to sleep seeing and wake up and see nothing. Fortunately, you can see that as early age-related macular degeneration occurred in only 16% of people, the late AMD occurred in only .6%, and the neovascular in 1.1%. Let me back up for a minute here and tell you just a little bit about the risk factors. Of course age is a risk factor, and I'll show you that again graphically. Gender, again we'll see women are disproportionately affected for neovascular. Smoking seems to be the most important obvious environmental factor that's related to it. 

And hypertension. It takes a while but before it rears its ugly head is a risk factor that you can find to be statistically significant. This is a graph of the prevalence data. Again, the tall bars are early age related macular degeneration. You can see that monotonic increase with increasing age. The difference between men and women is not so obvious, but it is statistically significant when you divide them by the wet and the dry type. And along the bottom, the smaller bars, the yellow and green, are late lesions. Again, very clearly age related. I'm sorry. So, aside from the smoking that I talked about in hypertension, there's also heavy alcohol consumption appears to increase risk. 

Chronic inflammation that's ascertained by doing studies, inflammatory markers in the blood appear to increase risk. For reasons that are not clear at all, sedentary lifestyle is associated with it in Beaver Dam. And the biggest thing that I put in larger font is genetic factors. And you may have heard about this recently. There was a big explosion about three or four years ago when a particular gene was found to be responsible. Estimates of how many cases it's actually responsible for is not known, but it's clear that will are many different genetic factors that increase the risk. Are there protective factors? Well, antioxidant multivitamins may reduce the incident and progression of late wet and dry AMD, and of course avoiding known risk factors will do it too. The antioxidant multivitamin preparations were tested in a clinical trial called the AREDS, the Age-Related Eye Disease Study, where there is random assignment to antioxidant nutrients and zinc or not, a placebo. And those people who had moderate degrees of age-related macular degeneration but no symptoms before, those people who took the experimental supplement had a 25% decrease in progressing to late stage disease. Not a miracle. 

About 27 people in the group who didn't get the medications went on, about 21 and the group that got it went on, but it's about a 25% reduction. You may know these preparations. They're commonly sold in any drug store. There are new treatments that have come on even while we've been in Beaver Dam over the last now 20 years. Avastin and Lucentis, which were drugs that were initially designed for and used for metastatic cancer, are used now by intravitreal injection, that's a needle to the eye, for wet AMD. This has provided some success. Now, it's often true that people need to come back for repeated injections which isn't fun and can be associated with infection or inflammation. There are other, they call them vascular endothelial growth factor inhibitors, or anti-drugs, but currently there's no treatment for dry AMD. It's an area of hot research, I can tell you, but there's nothing on the market now. So that's the end for macular degeneration, and I hope if you have questions we'll talk about it after. 

I'll talk a little bit about glaucoma. Now, glaucoma in Beaver Dam, which is very largely a white population, over 99% of the population is white. And glaucoma is a much more common disease in people of African heritage, African Americans or African Caribbean background. Nevertheless, it occurs in Beaver Dam. You can see once again the age trend, but of course if you notice the scale it's not nearly as common as the other conditions. In people who were 75 and older, about 5% of them had glaucoma. This is just a grand summary of the diseases that I talked about so far. So you can see that cataract is by far the most common condition. Cataract surgery was also fairly common, but it doesn't occur until later. Maculopathy, that's the same thing, the names vary by the time we made up the slide because of the trends in what you call things. 

It used to be called senile macular degeneration and that word was bad. [LAUGHTER] So now it's maculopathy or age-related macular degeneration, that's the same thing. It's the next most common. You can see glaucoma is not very common. And then just to show you how common visual impairment is and that has importance for quality of life and so on. So I'm jumping ahead now 15  years because the Beaver Dam Eye Study, the first round of exams was completed in 1990, but just in November, the last November, we finished the 20-year follow up. We don't have that data ready to go yet. So I'm presenting just a little bit of the findings from the previous exam which would be 15-year interval from the baseline for the follow up, 15-year incidence. So at the 15-year point, these were the primary causes of severe visual impairment in Beaver Dam. Now, incident means they didn't have this at the baseline exam. 

They may have had some impairment but they weren't blind. But 15 years follow up, 180 eyes had become blind or had visual acuity poorer than 2200. That's the big E on the top of the doctor's eye chart. You can see that at 52%, cataract leads the league. I'm sorry, AMD leads it for severe visual impairment. That's the 52%. Sorry. 12% were due to cataract which is very easy to obtain, if you will, in Beaver Dam. That's sort of a middle-class community, it's right here near Madison. 12% of those with severe impairment had a retinal vein occlusion. 

As I was mentioning before, it turned out to be much more common than we thought because this is quite severe visual loss. So that was news to everybody. 5% were due to a macular hole. Again, we didn't realize that was going to be so common. And then there are a variety of other things. What's notable is that diabetic retinopathy, which we thought was going to be a much more common cause of visual loss, is now responsible for about the same amount of severe visual impairment as is the retinal vein occlusion, and that's probably because there have been great strides, as you may know, in the care for people with diabetes. And tight glycemic control has really improved things remarkably for all complications of diabetes, including diabetic retinopathy but also cataract that occurs more commonly in people with diabetes. So this is a real giant step forward in medical care. At 15 years we were able to look at the incidence. We measured things at the baseline, we looked at the incidence of the new development of poor vision and we looked at the risk factors for it. 

Actually, I guess here I'm just going to tell you what happened to those people over the course of time. Not the risk factors for poor vision, we may get to that. But people who had lost vision were more likely to be placed in a nursing home. They were more likely, as you might expect, to have falls and fractures. We've got good history on that. They were more likely to give up driving. Many people give up driving because they know themselves that it's not a smart idea. But that's a big problem in Beaver Dam which is a rural community. Once you stop driving, you give up your independence. So that's a hard thing. 

It's a big change in life. And they were more likely to have a host of other medical problems. I want to just show you just a tiny smidgen about what happens disease wise over the course of time and why it's so important to have a longitudinal follow up. At the top you can see that when we first saw this person they had some early lesions of AMD. They had drusen, those are the yellow spots. The coloration of the photo is a little different compared to the others, but you have to just accept that people with different pigmentations have different color in their fundus. There's a little bit more at your lower left. And by the time you get to the picture on the right, which is in this case only 10 years from the baseline exam, there's a big patch where the retina isn't anymore but you can see a sort of white area and you can see atrophic lesions and you can also see some blood and that's from the new vessel. So this poor person has dry macular degeneration and wet. And what happens is that the central vision is lost. 

They tend to keep peripheral vision, side vision is good, but when you want to read something or if you're trying to track something you have a bad time of it. So, there was a very high incidence of late AMD of both varieties in people who were 75 years or older at the baseline exam. So in other words, it really gets to be a very significant cause of loss of vision as you get older. But it's not all bad news. At any specific age people who are born more recently were at less risk for developing AMD than those people born at an earlier time. And I'll try and walk you through a slide of this, but let me just talk this part out. For example, the five-year incidence, over a five-year course of early AMD in people examined when they were 65 to 69 was 14% among people who were born in 1918 to 1922, 10% in those people born just four years more recently than that, 6% again in those born in more recently, and 4% amongst those who were born in 1933 to '37. So there's a very step wise decrement in the incidence of new disease. That's a good thing. In other words, the way you would look at it here is that you can see the increased incidence with increasing age but at each age group in each set of four bars the people to the right-hand side in the group of four were born most recently compared to those at the other side. 

And you can see until about the last group when we run out of numbers that people who were born more recently have a systematic decrease in incidence. We don't know why that's true, we don't know what everybody is doing, presumably living better is good for everything, and it's probably true that many, many things have improved since the earliest decades. And we don't have any idea really what exposures in life, except for the few I mentioned to you, are increasing or have increased the risk. Well, I sort of gave you a whirlwind trip through some of the eye diseases, but the Beaver Dam Eye Study protocols have been borrowed by many, many studies around the world. There's the age study which is in Iceland, Andhra Pradesh in India, the ARIC which is an atherosclerosis study in this country, the Baltimore Eye Study, Barbados Eye Study, I could go on and on and on. I only gave you a partial list of studies that have borrowed protocols and other things and people who have come to work with us. So more data is available around the world. In the most recent Beaver Dam exam phase we have added an interesting new examination tool. Excuse me once again.  This is called an OCT. 

It's a really fancy gizmo. But it shows you, it's painless. You take essentially what's like a photograph, and you sit still and it shows you, in depth, the layers of the retina. So you can get a better idea of what's going on really. Let's see if I can get this to work. So you get a photograph like this and then using this fancy new technology, it takes what looks like histologic sections through the retina. Let's see, there you go. So it's taking five slices through the retina at different levels. And you can see, this happens to be a picture of macular edema or swelling in the macular area. And you can see where it balloons up that there are cysts that are filled with fluid, edema fluid. 

So we think this is going to be very important in trying to understand the development of some of these diseases.  Pardon me. This really concludes the part that I have about eye disease. I have a little bit more that I can present to you about a few of the other facets of Beaver Dam. If that's okay with you, I'll go on. So here's just something else about Beaver Dam. Falls are a big problem as I noted to you before. It costs about $19 billion annually for the healthcare budget to take care of the variety of things that are incurred after a fall. It's a sixth of the cost of the Iraq war. It causes fractures and all sorts of disability and, on occasion, even death. 

So falls are a big problem. Here are some of the causes that in the literature have been associated with falls. Some of them are just environmentally related. Some are gait and balance disorders. Some seem to be associated with vertigo or dizziness. Others, some people just have what are called drop attacks, they just lose consciousness. Some confusion. Some postural hypotension. In other words, you stand up quick, your blood pressure drops, boom, you go over. And then there are visual disorders that are associated with falls. 

As well as your garden variety fainting. And then some, they call them other, they can't identify the particular cause. But what are the risk factors for falls? It seems as though the weakness and balance deficits are the most common or the strongest risk factors, while the postural hypotension is less common. And then there are various things in between including cognitive disorders and mobility limitation. So it is my purpose to quantitate the risk of falls with respect to vision and other potentially modifiable functions in Beaver Dam. I used data from the 15-year follow up and, at that time, there were about nearly 2400 survivors from the original group and that was 77% of people who were still alive to come in. And we had complete data on some of the things I'll show you for about 2,256. We asked people, during the past 12 months have you fallen and landed on the floor or ground or fallen and hit an object like a table or a stair? If they said yes we asked, them how many times have you fallen in the past 12 months? We give them one fall for nothing. You live in Wisconsin, falling is not a rare event and it may have nothing to do with your disability but you could have an icy sidewalk like mine. So we give them one for nothing. 

But we used as our outcome two or more falls. And we looked at a variety of vision measures. Here are the ones that we had in Beaver Dam. We had what's called the logMAR, it's just a variation of the Snellen chart. Big dark letters at the top, small ones at the bottom. Then we used something called contrast sensitivity. And this gives you an idea of how people function in less than perfect lighting. And then we have a near vision chart which is also good to measure certain things. It certainly tells you a lot about how vision affects people's quality of life if they have trouble reading. We considered these all as measures of frailty. 

And we did a bunch of measures of frailty in the people of Beaver Dam. We did a timed walk. We had a course that was marked out, same for everybody, and we timed how long it took them to walk there. We did a chair stand. These, incidentally, are standard measures in studies of aging. We asked people to stand up without using their hands from a chair at a certain height of 19 and a half inches. We used a dynamometer to get grip strength. It's a very good measure in cardiovascular disease and other studies of subsequent cardiac events and also mortality. And then we did a peak expiratory flow rate, which is a poor man's pulmonary function test. And in Beaver Dam we are poor men and women. 

We depend on the largess of your Uncle Sam. Other things that are important, of course, are age and sex. We also looked at things that we thought would be related and they appear to be which were blood pressure, height, weight, waist and hip diameter, glycosylated hemoglobin. And we asked a bunch of other questions about other conditions. We asked about physical activity, cancer, cardiovascular disease, arthritis, other diseases and medication status. I won't walk you through all of this. These are just giving you an idea of some of the risk variables that we were interested in in Beaver Dam. Now, I want to walk you through this. These are four vision measures. Now I only showed you three of them before. 

The fourth vision measure that I include here is the walking around vision. In other words, people came in with their own glasses, the first thing we did was say read our eye chart. So we call that the walking around vision. Many people's vision could be improved, and that's the best corrected vision. We did that for distance and near, but we wanted to know how many people were actually walking around with suboptimal vision. At any rate, what you can see are four sets of three bars. The black bar in each is poor vision, and what you can see when you look up the axis, the Y axis, is that the black bar is taller than the others. In other words, people who did poorly on the best corrected vision far and near, the poorest walking around vision, and the poorest contrast sensitivity, all had a higher risk of two or more falls. We also looked to see if there was a discrepancy in the vision between the two eyes which we defined in a certain way, and we found that lo and behold if the two eyes did not see equally, the risk for falling was greater. It may be intuitive to some of you if you've had to deal with that, but not everybody is aware of that. 

We then showed here the different measures of frailty that I showed you before, and it shows that in each case they are bona fide risk factors for falls. People who could not stand up from a chair without help, people who took the longest time to walk our very short course, people who had the poorest hand grip strength, and those with the poorest pulmonary function all were at increased risk of falls. We put together an index of all these measures and we called this a frailty index and you got one point for each bad thing you had. So either if you had a poorer measure on any one of the vision tests, if you couldn't stand from the chair without using your hands, if you had the slowest time to walk the course, the poorest hand grip strength and the poorest pulmonary function. So we had a scale that went from nothing wrong to all five of them wrong, and you can see that the greater the number of frailties the more likely you were to have a fall. Other things that were also related to falls are things that you might find intuitive. People who are older were more likely to fall. Women were more likely to fall than men. If they had two or more what we call co-morbidities, other illnesses that we could identify, cardiovascular disease, cancer, arthritis, whatever, two or more had increased risk. And then medications, this is a very interesting one, but people in Beaver Dam take a lot of medications. 

And you can see that there's an increased risk of falling with an increased number of medications. Now I don't know if it's the medications or the reason that they're taking them, I can't be sure. We didn't have enough in any one class to be sure. Things you worry about of course are sedatives and things of that sort, but there are many others, blood pressures medications and on and on. Things that we thought might be related that weren't were use of vitamin supplements, some specific medications like sedatives, statins were not protective, hormone replacement therapy which some women were still taking at the time, physical activity didn't come in, neither did portliness, body mass index or the waist/hip ratio, and blood pressure didn't either. Well, in any study you do there are limitations, things that you would liked to have done better or you couldn't afford to but you thought was bad. We, for example, didn't have a measure of cognition, which I think is quite important. And also people who had very bad diseases didn't participate. You had to be able to do all these tests in order to get counted, and people who were quite severely disabled couldn't do all of them. So my conclusion is that people with poor visual function had a higher frailty score and had an increased risk of history of falls. 

I think the frailty score may be a good measure to evaluate persons at increased risks of falling. And something can be done for some of these. Physical therapy can help for some of them, not for everything. But also doctors paying attention to medications and so on and counseling patients would be helpful. So longitudinal follow up, I can't emphasize enough how important having long-term measures is for understanding many of the problems here. As I said, we had baseline evaluation from '88 to '90 and we had reexaminations these many times. And we're very excited about getting to the data analysis, but that's a big step yet. We still have a lot of work to do. This will allow us to calculate change over time, incidence of new diseases, we add other risk factors that have become more and more important over the years. We've added some protocols that will give us more information like the OCT. 

Did we do anything good for the people in Beaver Dam? They've been very good to us. They've been a wonderful population to work in. But we did diagnose 90 people with diabetes who didn't know they had it, 947 people with increased cholesterol, 124 with significant carotid narrowing, that is not done directly in the Beaver Dam study. There's a parallel study on hearing where they got funded, we didn't, to measure the carotid artery narrowing. And we found that 729 people had hearing loss, all of whom did not know that they had the condition. So the border implications of the Beaver Dam Eye Study is that we have estimates that are used nationally for disease frequency, and they've been published in a variety of ways. As I told you, we freely share our protocols so there can be international collaborations and also we can compare across countries which sometimes is very insightful. And the incidence studies and the cohort have provided increased information on the incidence and changes over time, as I mentioned before. The Beaver Dam Eye Study has expanded. It started out as an eye study. 

Now, as I mentioned, we have a hearing loss component which is also where they do the IMT or the carotid measurements. There's also a health outcome study, finding how sort of quality of life issues amongst these people. We are hot now on genetic studies of all the age-related eye conditions, and this is really a very, very promising area of research. And I guess that's about it. I thank you very much for your attention, and I'm more than happy to take any questions you might have. [APPLAUSE]