Physical Activity and Vision Loss–Bidirectional Causality


>>So thank you. Just a reminder, if anybody came in, we do have a paid for lunch that’s complimentary for the attendees and it’s a boxed lunch. There’s a room next door,
we’ll be able to do that. We’re gonna have some
discussion during lunch as well. There’ll be some time for networking. Fascinating, the multi-system effects of exercise that have
been discussed already. You’re gonna hear that in some more specialties this morning. We were excited to have a
multi-disciplinary group. We’ll get started with our next session with Dr. Ramulu from Ophthalmology. He’s the Director of the Glaucoma Service and will be addressing us about physical activity and vision loss. Thank you Dr. Ramulu. (audience applauds)>>Thanks for having me here and our wonderful talks already
today, I really enjoy them. Dr. Bama, that was really
a terrific lecture. I look forward to hearing everything else that people have to say as well. I think exercise is something which is funded mostly at the national level and not at the corporate level. These are my disclosures as well. I think we’ve talked a little bit about how to measure physical activity. I know Dr. Schreck will probably mention it in much greater detail. As well, going forwards. But generally for our research and all the research I’ll
talk to you about today, we’ve used accelerometers. This is the one that
we use, called Actical. Though I’m not sure that it’s uniquely capable of doing what it does. I think we’ve generally
used it as something to evaluate how much time people spend at higher levels of activity. Either moderate or
vigorous physical activity. And people have shown
reasonable correlation between measures generated
by accelerometers and the gold standard,
which is energy expenditure. Ultimately, this is much more
related to most of the work that’s been done, at least
in vision, prior to our work. Which has really looked at
self-reported physical activity and if you look at the relationship of self-reported physical activity as opposed to objectively
measured physical activity. With regards to things that
we all know are associated with activity such as
BMI, triglyceride levels, a blood glucose, skinfold thickness, than the actually measured activity, is much more associative. This was probably the work that really got us started into physical activity. It was the result that
really surprised us. We were actually looking
at the NHANES study, which is a national on-going study. For a few years, they actually put in accelerometer measurements. We were looking at the
association of vision with activity restriction
and as co-variants and other things that were in the model. We actually included some
other variables as well. We found things such as COPD and arthritis decreased activity about 10% to 15%. Things such as diabetes and stroke, in these community-living individuals, decreased about a quarter. Our patients with congestive heart failure were down by about a third, and people who had worse vision, not blind but just poor vision, were down by a half. So it was actually the strongest
predictor of low activity amongst all the things
that we could study, which was very surprising to us. Oh course, poor vision doesn’t
come in a single cause, there’s a few different causes. Some of it is caused because
the shape of your eye is wrong. Typically, because you read too much as a child and you’re now myopic. This is because your eye is too long and so you have myopia, which
is a type of refractive error. Another word for that is near-sighted and of course this can be
corrected with glasses. If you actually look at
what was the affect of, or the association of
physical activity with this type of error on also
an uncorrectable error. You actually see people
who just needed glasses did about the same amount of activity as people who didn’t have any eye disease. It was only really the
people who visually impaired. Meaning they actually had
an eye disease limiting their vision, that really
restricted their activity. Of course, visual impairment
is not poly homogeneous either. There’s many reasons for it, there’s some things that can be corrected very easily, such as a cataract. There’s diseases such
as diabetic retinopathy or macular degeneration, and other diseases such as glaucoma. We found that in some of these very specific diseases, as well, people seem to restrict
their physical activity. This is one study that
we did hear at Wilmer where we found that as compared
to people with normal sight, those with age-related
macular degeneration did 35% less physical activity and there was a dose response. For every line of visual
acuity worse they were, they did about 12% less time in moderate or vigorous physical activity. We also saw the same thing
with diabetic retinopathy. Although we flipped the
analysis in this way. We saw that the people who were diabetic were more physically active, were actually less likely to
have diabetic retinopathy. In females, even just an extra 10 minutes of moderate or vigorous activity a day, really decreased the chance that people would have moderate or severe
retinopathy by three quarters. These effects were
independent of those things that you know affect diabetes as well. Such as disease duration, blood
pressure, or hemoglobin A1c. Of course not everything affects vision through visual acuity. Visual acuity is what you go to and see when you go to the doctor. So you read down the
chart with increasingly small letters and they give you a number. So 20/50 means that you see at 20 feet what a normal person would see at 50 feet. In other words, you have to
be closer to it to see it and a normal person would be 20/20. So they see at 20 feet what a normal person would see at 20 feet. There’s other types of
vision loss as well. I’ll talk to you about one of
those in particular, glaucoma, which affects your field of vision. So it’s actually tested with
something called a perimeter. It measures the perimetry of your vision. It sees how bright they have to show you lights for you to see them. Areas that are shown in black over here, means that the person
had to be shown a light brighter in that area for them to see it. Meaning that they had damage to that portion of their visual field. It’s graded on a decibel scale
from zero to negative 30. People in this NHANES data set also, if they had visual
field loss in both eyes, also restricted their
activity considerably. If you had visual field loss in both eyes, as compared to those with normal sight, you’d have 30% less physical activity. This is again in the ballpark of a lot of pretty substantial diseases that you would think would
be much more disabling, with regards to physical
activity, than eye disease. We did the same study here at Wilmer. We found that as your
visual field damage was, If your visual field damage was worse, you took fewer steps a
day and you also engaged in less time spent in
moderate or physical activity. Our initial assumption was that, activity restriction in eye disease was due to impaired mobility. Unlike other diseases
where you can’t walk, vision is not a actual
physical impairment, you can walk. Then we thought that maybe
the real reason behind this is that people are choosing not to walk, because they feel like they’re unable to or that they’re unsafe doing so. So we decided to go about this by looking at their fear of falling. Instead of asking a single question, we actually used this
University of Illinois fear of falling index. This asked people questions on, ranging from things that
are very challenging, such as fear of falling
while walking on icy ground, to dark stairs, to a moving bus, to things that should be
fairly simple for them. Just going for a walk or
getting in and out of a car and picking up an item off the floor. I think with this technique
called Rasch analysis, you can actually pair people up and pair them on the same scale as the difficulty of the item. This methodology grades the difficulty of the fear of falling items and also grades the ability of the people, and through that gives people a score. We did find that people with
both macular degeneration and with glaucoma, had a
greater fear of falling. The score is shown here in logits. It’s an arbitrary unit, log-odds units. So people who had glaucoma,
had greater fear of falling. As demonstrated in a lower logit score and again there was a dose response. So the more of your visual
field that was damaged, the more fearful you were of falling. It’s always nice to calibrate
these effects to other things that were in the data set as well. So if you had an additional
comorbid illness, these were comorbidities which we thought generally affected mobility, that this was about equivalent
to about a five decibel loss. Which is maybe about one-sixth of the dynamic range of this disease. Our question was, well is
this really what seems to be accounting for why people
restrict their activity? In age-related macular
degeneration patients we did this mediation model, where we looked at whether the association between poor vision and physical activity was mediated by the amount of
fear of falling people had. Indeed when you added fear
of falling in the model, that association between
vision and activity went away. It seems like maybe that was the cause for this particular disease, age-related macular degeneration. However when we looked at glaucoma we didn’t see that affect. So you had again, an association between now visual field damage
and physical activity and when you added fear
of falling in the model that association did not go away. Nor did it go away if we included other things such as driving cessation. So then we started getting
the idea that maybe, “Is the direction of
causality the opposite “of what we were thinking?” Is it actually, not
necessarily that people are less active because
they have their eye disease? Is it that they have their eye disease because they’re less active? We started looking back
at the literature on this and indeed there was a study done that looked at a large
population of older male runners and they found that the
incidence of glaucoma decreased with how quickly these runners ran. So, Dr. Fickey I think
you’re probably safe here. Especially if you, at least from glaucoma, if you actually had men who were running a 10K some time in their life at greater than five meters per second. In these 800 men, actually none of them, for a very prolonged period
of time, ever got glaucoma. Many of them would have otherwise since it’s a fairly prevalent disease. You do have to run pretty fast. You have to run each mile in
five minutes and 21 seconds, and the 10K in 33 minutes. So it’s not for everybody but these people are very safe. People also show that in mice you can protect age-related IOP damage, or intraocular pressure damage. These are young mice who are
subjected to high pressure. High pressure is the insult
which can cause glaucoma. If you do the same thing to older mice then you see that their electrical signal from the retina goes down. In other words, their retina’s being damaged by these high eye pressures. However, if you take those older mice and you force them to run on a treadmill, then basically you protect
them against that damage. We started asking, “Could exercise actually serve “as an effective treatment for glaucoma?” And I think this is important. It’s the second most common reason for irreversible vision loss worldwide and accounts for 4% of
U.S. physician visits. Right now there’s actually only one treatment for the disease. There’s many ways of
accomplishing that treatment but ultimately it’s only one treatment. So this is true, it will actually be the second treatment for this disease. I was also motivated by this. We started getting these ideas and I ran it by one of my patients and she was a 32 year old with glaucoma. I said, “Well you know…” She was convinced that her
vision was getting worse and she said, “Doctor is there
anything else I could do?” And I said, “Well there’s this idea “that maybe exercise might
be able to protect you.” And so she said, “I’m doing it. “I’m going to start running. “I’m going to run five miles a day.” And so she started and then
what we actually noticed… This is the percent of her vision, of her field of vision that she has. It started going up. Then she stopped and it started
going down a little bit. She restarted and it went
up a little bit more. She stopped again and it went down again. This is actually continued on
and every time she comes in, I can tell whether she’s
exercising at that time. It’s pretty remarkable. In fact, we saw the exact
same pattern in the other eye. So rather remarkable. We’ve also shown more recently, that the glaucoma patients
who were more active don’t worsen as quickly. We only examined their physical activity at one point in time, and then we examine how quickly the disease changed or didn’t change. Either five years before
or five years after this one week activity assessment. We found that patients who are more active have slower progression, and these effects were
independent of other things that have been known to
affect disease worsen, such as age, race, disease severity, or the pressure within the eye. We still don’t really know what the direction of
causality is, however. So if you look at the
entire period of time, we do notice a positive effect. A positive number means that they don’t get worse as quickly. If you look at just the period of time before the activity assessment, however, you also see that there’s
a positive association. So in other words, if your
visual field is worsening, you can say that you’re less active. You also see the same effect afterwards. You can say that if you were less active you have less visual field loss. Even though we have
this longitudinal data, we still don’t really know what the direction of causality is here. We started with Dr. Stewart
and Dr. Schreck here, who you’ll hear from today as well, a study called Visual Improvement in Physical activity Study, or VIPS. So it’s a single-armed pilot study with 35 glaucoma patients who are doing a six month walking regimen and the primary endpoint is
visual field improvement. So this is a somewhat novel idea, that you can actually improve peoples vision in this disease. It’s always been thought to be something which is purely degenerative, as opposed to maybe something
which is regenerative. There’s a multi-pronged
intervention to improve activity. We started out by asking
them to self-motivate, give us three reasons for wanting to increase their activity. They’re given a Fitbit charge, so they can see their activity as they go through their week. They’re given weekly step targets. We take them from where they are and increase gradually up
to 10,000 steps or more. And they’re given one or
two text messages a week so they are encouraged to continue. And then we check in on them monthly to go over how things are going, the review with them why they wanted to participate in the first place, and to really encourage
them to be more active. These are some examples of some of the messages they are given. Sometimes it’s just giving
them them their goal. Sometimes it’s congratulating
them on beating their goal or encouraging them if they
didn’t get their last goal. Some specific strategies
about what they might do in their daily life to
maybe meet their step goals. So just going on walks. Also other things that are more practical, like parking your car furthest away when you go to the parking lot. I think our goal is to really see whether exercise can be a viable
treatment for eye disease, and we’re using glaucoma
as a model disease there. I think there’s very
strong preliminary data for this in both humans and mice. I think that it’s great
to hear all the work today and Dr. Bama’s work, which gives a model for really increasing activity. So that we can really
test these hypotheses in a very rigorous way. In the result would be a very novel way to care for diseases, which
have few or no treatments. In addition to glaucoma, there’s some data that some of these
neurodegenerative conditions, such as retinitis pigmentosa, for which there’s absolutely
no treatment at all, might actually respond positively
from physical activity. It would actually be the first
treatment for that disease. I’m happy to take an
email or any questions and thanks for having me. (audience applauds) Yes.>>Audience Member: I know this is outside of your topic but, do you
care to comment on the (microphone cuts in and out)
presented in Ophthalmology (microphone cuts in and out)
generation X to increase in men who participated
in vigorous exercise?>>Yeah, I reviewed a similar paper for that in glaucoma as well. I think it was self-reported data and I think they had these cut offs where they were looking at
different categories of activity. So they really only found the effects somewhat arbitrary cutoffs
that they really exercised. They self reported exercising everyday. So is it a dose response curve Or is it a U-shaped curve? Where at some point, if
you’re doing too much, it’s bad for you. But I think most people
probable aren’t at that level. I’m guessing then most of the effects, positive effects will
be on the early stage.>>Audience Member: Is there
any biological possibility?>>No. Not that I can I think of. But it’s possible that it’s true. And I’ve heard anecdotally,
people say that ultra marathoners and people
who are extraordinarily active might actually get some of
these diseases more often. So I wonder whether it’s not
picking up people who are way out of the extreme
end of the spectrum. Yes, yeah.>>Audience Member: So
do you know of anyone who’s actually looking
at the acute responses to exercise to the eye and understand how
exercise training long term modulates the risks of different kinds of disease progression?>>No, that’s a great idea. We thought about doing
some of those experiments. The eye does give you a window to look at some things
which are fairly unique. So there are systems, for example, I’m looking at them like either arterial or venous oxygenation
levels in real time, so just with a picture. You can also, just now, you can take an inch a gram of the eye directly as well but it doesn’t actually
measure flow that well but it does measure the branching distribution of the retina. And so it can give you
the density of the vessels within the retina and it can do that in the layer specific fashion. I don’t know, maybe you can
answer it better than I can whether some of these things can change. I think definitely the
oxygenation levels can change. I don’t know whether you can
actually see vessel growth in response to an exercise program but that would be a fascinating question. (audience member speaking inaudibly) Yeah. We haven’t. No, it’s a good idea too, though. Great. (audience applauds)

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