Mr. Andrew Iwach: What I'd like to do and I've been asked to do is kind of give you an overview of how we look at SLT, how we use SLT in our patients in San Francisco. We're currently I think one of the largest groups of glaucoma specialists in one location on the West Coast, certainly in the United States

I work with a number of different companies from pharmaceutical to laser to device to diagnostic. If we end up into an area where there's any conflict of interest, I will disclose that as best as I can

With that said, I always like to kind of start off and talk about really what we know, but how we look at glaucoma patients. And I like this slide because I've seen it so many different times. It's from the OAT [sp] Study, which basically showed something that we already knew, that if you take large group of people and they have elevated eye pressure, if you treat them, it reduces the risk of damage to the optic nerve or change in visual field

And that's usually the message that you walk away with, and that's okay

But, if you look at the data in a slightly different way, we have a slightly different impression. So, it is true that if you treat patients, the number of patients in this red area decreases, the number that are changing. But, I'll point out that over 90--around 90 percent of the patients in this carefully monitored study with elevated pressure did not progress, and that's the point

The most common form of glaucoma, open angle glaucoma generally moves slowly. And our job, our job as ophthalmologists is to take a look at the patient, take a look at the eye and figure out what do we need to do today to make sure that that patient continues to see for the rest of their life

And so that--in lies the question. Whatever we do today can impact their quality of life. What's the best choice for that patient

Now, we don't know how long patients will live. And this is our US tax dollars hard at work. This is from 2001. It shows some life expectancies

Now, I'm not suggesting that you bring out a table like this and Mr. Joan [sp] comes in, sir, you're 60 years old, you're Caucasian--because it doesn't work that way. People live--your most difficult challenging patients never die. The nicest people - I call it nice person syndrome - seem to get all the bad cancers

But, age does influence what we do as we try to figure out the best solution for patients

Another graphical way to look at this--this is actually from Dr. Spathe [sp], and it graphically represented what I was trained when I was a fellow with Dr. Shaffer [sp] and Hoskins [sp] and Hetherington [sp]. This graph shows that we're born and we die. And if--again, if you have a way around death, let me know. Green is good, red isn't so good, and you don't want to cross this line

Now, in many comprehensive ophthalmologist practices, there'll be older patients whose optic nerve are pretty good, and they don't have that long to go. We have those patients in our practice, but we also have younger patients who have very damaged optic nerves

So, our approach to this patient--this patient could lose vision on our watch. But, there are a lot of patients that fall into this category

And so, as we look at alternatives, what we need to do is tweak the system, not necessarily cause all types of problems for that patients upfront

Now, there are lots of different types of drugs and certainly, in the last 15 to 20 years, a lot of new entrants. It would have been a great time to take your board exams about 1960 - not that many questions to ask about

Now, if you look at what we're doing, we're currently--this is US market share. This goes to 2008. The prostaglandin analogs are the most commonly used class of drugs in the United States, and in fact, in most countries. The crossover occurred in the US about 2003, 2004

We use them because this is our best drug. It works, and it has the fewest side effects

Well, really, there are side effects from even these drugs. You know, patients, all types of occupations are affected if their eyes are red

Now, the lashes for most people are fun but not for everyone. And as a surgeon, we can cut through these blood vessels that can be induced by, you know, this hyperemia, but it's just not a lot of fun. And that is our best drug

Well, beyond the drug itself, how is the patient actually gonna take it. There are lots of different factors why a patient may not take their medication from side effects, the--it's--you know, I'd like to think all of my patients are ideal and always take them. But, in the United States in particular, economic issues are more and more becoming a problem

The co-pays for the visits, the co-pays for medications are getting higher. So, no matter how good a drug is, if a patient can't realistically every day get it, you run into problems

Now, some of my patients are very creative. These are all true stories. One of my patients said, you know, I'm gonna treat my heart one month, I'm gonna treat my eye the next month

Well, I don't think that's the right way to approach it. The data I showed you actually has some support from real clinical research

This is refill rates when a patient is given a prescription. What are the odds that that patient will refill that prescription

And if you take a look at the different types of diseases, glaucoma is here in this yellow line, and the statin therapies are here in this magenta line, and they kind of line up. This is years, this is months

So, at about six months, roughly around 50 percent of the patients are not refilling their medications. Both the statin therapies as well as glaucoma therapy have some common elements. These are problems that patients upfront at that time do not perceive. They don't see it as a problem, so why should I take that drug

So, it's not only a theoretical problem, it is a real problem. And so, do we have a solution to help these patients that gets around these challenges

Now, there are all types of new delivery systems that are being looked at for more sustained drug slow release over time. But, they're not yet available. And yet, it also doesn't walk away from the side effects of these medications

Well, maybe we should just operate on everyone. Let's make holes in their eyes

As a glaucoma surgeon, we're excited. My goodness, these are successful blabs [sp]. As a bacteria, these look like ski slopes

Our strong anti-scarring medicines wipe out the blood vessels, which helps these blabs continue, but that's our defense system. These are weakened tissues

So, you can take an asymptomatic patient with a field loss who's all happy, take them to surgery, induce some blurred version, they got unlucky, they get an endophthalmitis, they can lose vision or lose the eye - not a good game plan. So, although we do surgery when we have to, that's not our first choice

And ophthalmitis we can help. Patients are instructed to try to identify it early on. But, surgery as a first line really impacts their quality of life, which then leads us up to laser therapies

There are lots of different wavelengths that have been looked at over the years. And to some degree, many of them will lower pressure

But, the question is what's the best characteristic. And the trend that has been followed over the last 10 to 15 years is can we find a laser that reduces pressure but minimizes collateral damage

SLT falls into that category. And I'll show you a couple of graphs to kind of give you the characteristics of how it works

But, essentially, the spot size is nice and large. It is a calumniated [sp] beam, so the focus should be close, but it doesn't have to be precise as it did with ALT, for example. The unit itself is quite sturdy, it's air cooled. And it allows for the selective treatment of the trabecular meshwork

We've had a chance to utilize this type of system from Ellex. It's very durable. It's really a nice platform, comfortable for our patients

Looking at the different wavelengths--so, for those of you who still may be doing something like Argon laser trabecularplasty, SLT, the wavelength is very similar. The main difference is the pulse duration is much shorter

And by doing so, you reduce the amount of energy, and that's why you get less of the collateral damage

Specifically, if you take a look at the energy levels between SLT and ALT, you're looking at a ratio of about one to 100 on average. But, the concept of fluence, because you've increased the spot size, so the density of energy is way lower, one to about five to one to 6,000. And that's why you don't see the collateral damage

You know, depending on which study you look at, in histology, even probably in the back there, you can see that, with ALT, you end up--you can visibly see a change to the tissue when you study it as opposed to respecting the underlying architecture with SLT

The technique is pretty straightforward, utilizing a lens. And they have a variety of different lenses that are available to do this

You obviously want to utilize the trabecular meshwork. And, again, this is something you use a helium neon aiming beam to determine where the laser energy will be then applied

There are certain situations where you have to be a little bit more careful. The speaker just before us talked about narrow angles. And you can treat narrow angles. Typically, you're do a laser iridotomy to try to deepen it

But, you want to turn--you know, adjust the lens, have the patient look towards the mirror so you're making sure that you're treating the trabecular meshwork, and it's certainly doable. You just have to be aware of it and treat the correct area

As far as how the protocol has changed over time--you know, way back, I was asked when did we start doing this. I think it was probably in the last '90s that we did our first SLTs. And something I learned from senior associates, they--with ALT, you use a lot more energy. These guys get more irritated

And--but, yet, they would often say, you know, we don't want to use corticosteroids. We don't want to use Prednisolone Acetate, because they felt that those patients did better

The current theory on SLT is that there is this inflammatory component at the basis to how it works. But, the big news is that with SLT, since we're using so much less energy, almost always--actually, pretty much as a routine, I do not give post-operative anti-inflammatory medicines.

I tell the patients that you'll feel a little bit of light sensitivity for the first few days. That's good. That means the laser's working

Occasionally - occasionally means once every two years - I'll get a call from a patient, and it really bothers them. And I say, no problem, we'll give you a topical non-steroidal anti-inflammatory

But, I instruct them when I do the laser, say, you know what, if we can avoid these drugs, the odds are you may have a better result. And almost always, they understand that, the light sensitivity is tolerable, and we avoid them

You know, some people treat 180. Many of us treat 360 with every treatment. We could talk a little bit about some of the different parameters. But, both settings can work, depending on the patient's need and their profile

Some data - I'm not gonna give you a lot of data. You--for any of you who've been in this space, you know - this is one of the first studies that compared SLT with ALT. And I'll also point out I put flags there. And the reason I did is whenever you have any device or treatment that all the data's coming from one site, they may be on the mark, but it's nice to hear different locations, different parts of the world all coming up with the same basic results. It certainly gives us more confidence that what we're seeing is correct

So, SLT, ALT, the results very similar--how does it affect--the state of the disease influence things? Well, if you're earlier on in the treatment algorithm, on average, you'll have more of a response

So, if you have patients on three medications or four medications, you may see some result, but it won't be as dramatic as if a patient is at ocular hypertensive or has not been on other treatment before. But, in each of these categories, you can see some benefit from SLT

One of the studies we looked at was if someone had had ALT before and it was 180, if you treated one eye--side or the 180 that had been previously treated, we found a little bit of a difference if you treated the untreated 180 degrees. But, even if they've had prior 360 degree ALT, we did see some response from SLT in these patients, as well

Looking down, can you repeat SLT? Why didn't we repeat ALT? The reason was, with that higher energy level, your risk of IOP spike was higher. That's why, for those who were doing ALT, they would never go back

With SLT, there's always a small risk that you could see with any laser procedure an IOP spike. But, in my experience, it's just very uncommon

And there--basically, I'll show you a couple of slides looking at the data on retreatment. And the bottom line is is that it can work. It may not work quite as well. It may not last as long. But, if you have someone who's 85 years old or 80 years old and you can keep them off of medication or reduce a medication for an extra year or two or three, that is very statistically significant to that patient. And so, as a tool, it's been useful in that setting, as well

And, again, here's another study looking--similar results that when you repeat it, the pressure lowering is there. It's maybe not quite as dramatic, maybe not quite as long, but it can also work in that setting

Now, primary therapy - there are a number of centers in the world that have looked at this data. This is from Norway looking at open angle and also the sub-unit of exfoliative glaucomas, also showing that, going out a few years, the pressure lowering effect is seen from their study as primary therapy

Another study, which is interesting, out of England, looking at comparing medications versus SLT--and if you look here at this data point at one year, SLT and a prostaglandin analog in fact are very similar

And so, if you're looking for data to support using as primary therapy, it's published, it is available

Looking at another part of the world out of Israel, similar results - primary therapy, showing that it drops intraocular pressure and can keep the intraocular pressure down for quite some time

Another study, another center, similar results--and so, again, that's what I like about it, that we have different areas of the world, different populations, and yet basically the same general pattern in the data

Well, here in the United States, what are we doing? Well, this was recently published just a few months ago in September. This was a comparative study looking at SLT versus medication as initial treatment for glaucoma - J. Katz [sp], really a great researcher here on the East Coast

What they did is they took--they had 18 different sites. They had patients with elevated pressure. And then, they were set into two groups

The algorithm was interesting. In the SLT group, they initially received 360 degrees. If they needed more, the next step was 180, then 180

In the medication group, they were started on a PG analog. If more help was needed, they then went to a beta blocker, and then they went on from there

So, when we look at the success criteria from this study, there were two issues - how did they do on pressure and how many steps were required to get that pressure down

So, what does the data show? Well, if you look at medication versus SLT, the numbers are very similar

So, on their ability to lower pressure within this study, in fact the two were comparable

But, if you take it one extra level, the final conclusion was that, although the results were similar in IOP reduction for both groups, there were more steps required in the medication group. So, certainly, they're in the same ballpark, but you were able to be more efficient by using SLT

And so, that completes the world tour of data back here in the United States and very current

How about cost? Is the cost--you know, when cost studies come out of Canada--and I don't live in Canada, but from what I understand, their medications are a little bit less expensive than in the US. And that's what drew my attention to this study

They took a look at patients and did an analysis on SLT on a couple of different scenarios - if SLT was working for two years, if SLT was working for three years, if glaucoma patients were on one drug, two drug or three drug, how did the numbers stack up

Well, in my opinion, if you're saving money in Canada, then you're gonna save money certainly in the US. And so, no matter which category you looked at, a more conservative view of SLT or a longer view of three years, the patient ultimately--and our society is really what saves money in treating this and managing this disease

What are we doing in the United States? This is Medicare data, and I'll draw attention to a couple of lines. This light blue line here reflects LTP. That includes SLT and ALT. My suspicion is a lot of this is SLT. SLT was introduced in the United States just about this time

I'll draw your attention to this darker blue line here. This is the number of laser iridotomies being performed. So, again, it's not a perfect metric, but kind of gives us a sense that the patient population is aging, and this is increasing a little bit - nothing like LTP

The other line I'll show you is trabeculectomy. That’s the red line. And this has dropped off

Now, interestingly, why are the--I can--we don't have causative data, but we have certainly interesting associative data that the prostaglandin analogs came into the United States about here, SLT comes in about here

So, when we go to these meetings and we sometimes ask does it matter, it sure does because these type of developments have really changed what we do. And I think they've changed it for the better

Patients are not having to go to--having filtering surgery as often, and we're able to control it with these newer tools such as SLT

So, common questions I get asked - you know, do I offer SLT surgery--do I offer SLT after surgery has not been successful. Some patients will respond to SLT, in my experience, even after filtering surgery. So, it is an option

So, pretty much, every stage of the disease almost is contraindicated with inflammatory glaucoma or neovascular glaucoma. Certainly, it's something to consider

Do I offer as a primary therapy first off? I have a discussion with my patients, and the patient--in my experience, I get better agreement, compliance with the patient when we make the decision together

And I'll compare the two. I'll say we can go medication or we can go laser. And they'll talk about laser

In California here, we're all--they think about Star Wars. These are military devices. No

What we're going to do--I borrow from our plastic surgeons the terminology - we're going to rejuvenate your trabecular meshwork. We're going to enhance its ability to work. We're not gonna make a hole. And if I have to go back and do more laser, we're going to enhance it. Well, maybe that--but, there's--you could--you want to frame it correctly so they understand because they're thinking you're boring a hole with this thing

What you're really doing is you're tweaking it. We're causing some local inflammation so your own cells can help the other cells work better. And if they understand that, they often gravitate to that

Some patients may be a bit afraid. That's okay, no problem. Let's try you on medications for a couple of weeks. Then, they come back. How ya feeling? Problems with a red eye? How's your energy level? Did you actually take them

So, eventually as--every patient has their own process as to how they come to the conclusion. But, most patients would like to have a try of the SLT

I've talked to you about that. And as far as the role of SLT down the--in the future, it's a great tool. I mean, there's no question

And having it available--I think the data itself from our Medicare data shows availability of the laser treatment, we're using it, and most importantly, we're at least delaying if not avoiding filtering surgery in these patients

As far as standard of care, certainly in our community, that's all based on communities, but having it available, giving an option--this was about ten years ago, I was chairman of the department at one of the hospitals, and we had--there was a debate. Should there be SLT, ALT, should we have both

And there was some who said we don't need SLT. But, the hospital, we were able to convince them to buy a laser

So, we had an Argon--we had an SLT side by side. Within six months, all the doctors who told me we didn't need an SLT had called me to find out how to use the SLT, and the Argon was being used not at all

So, from a single anecdotal uncontrolled study, I know that if you put the two lasers side by side and both are available equally to ophthalmologists in California, specifically San Francisco, they migrate to SLT

And, you know, when you look at all this, there are lots of things that you want to consider - the side effects, compliance issues with medications. We've talked about the selectivity of the laser. It's a smart way to manage this disease for these patients, minimizing their impact on qualify of life early on

But, ultimately, after all the data is looked at and all the discussion, what would you do to yourself or what would you do to a family member

I know myself, I don't want to have red eyes seeing patients. And I'm pretty active. I'm not that excited about a beta blocker. And I actually, at night, I'm not gonna remember to do something every day. So, SLT for me personally makes a lot of sense as it does for a lot of my patients

Well, if you have any questions, we're in San Francisco. We're easy to find. Always feel free to contact us

And are there any questions?