Dr. Tony Realini: Today, I'd like to share with you a little bit of information about a project that we've been doing in St. Lucia to address the glaucoma burden there

Let me begin with a few disclosures. I am a consultant to Alcon. And I do receive research support from Lumenis for this project

St. Lucia is a small island nation in the Caribbean in the West Indies down in the southeast area of the Caribbean. In the 1980s, there was an epidemiologic study of glaucoma conducted in St. Lucia with funding from NIH and under the direction of Roy Wilson [sp] and Roger Mason

This study revealed a prevalence of glaucoma of approximately 8.8 percent in people over age 30

Ten years later, the same research team went back to St. Lucia and reexamined the patients who had been previously identified with glaucoma and found a 10-year incidence of glaucoma-related blindness of 16 percent

This is untreated glaucoma. And these numbers represent the natural history of glaucoma

When the initial study was done, there was a treatment plan set up but with changes in the government structure soon after the completion of that first study, those funds were reallocated. The treatment didn't happen

And so, the 10-year incidence of glaucoma-related blindness represented on this slide is the untreated rate. That is natural history

Treating glaucoma in the developing world is challenging for a number of reasons. Medications are impractical in part because they're not always available and in part because they're not always affordable

Surgery for glaucoma is effective certainly but not tremendously so in the developing world

For cataracts, a surgical mission is feasible in the developing world. You can swoop in, do 100 or 200 cataracts and go home. And they'll all heal up pretty well without significant postoperative care

Trabeculectomy, however, is not like that. If you go down and do 50 or 100 trabeculectomies, the postoperative care required to make those work for the long term will require that the surgeon or someone skilled in trabeculectomy postoperative management be on site for months afterwards. And that's the problem that limits the role of surgery

There are very few if any eye care professionals in these areas who are comfortable managing postoperative glaucoma

These observations were the rationale that we used for thinking about trabeculoplasty as an intervention for the glaucoma burden in the developing world

Trabeculoplasty has a number of features that make it potentially useful in this setting

It is essentially fire and forget in the sense that there's no significant postoperative management required. There's no need for postoperative care. There are really no drops that need to be taken or examinations that need to occur for safety reasons afterwards

It can reduce or eliminate the need for daily medical therapy if it is effective. The technology is portable. The treatment is incrementally inexpensive once the technology and the expertise to run it are on site

And as we are learning, slowly but surely, through the literature, SLT may be repeatable so that, even though it does wear off over time, we may be able to sustain glaucoma management with repeat SLT

SLT was developed a little over a decade ago. And most of the studies in the literature to date are from primarily Caucasian populations in the U.S., the U.K., and throughout Europe

There a handful of African-derived eyes in these studies. But, none of them enrolled enough African-derived eyes to allow a separate analysis of these. So, we really don't have much information on the safety and efficacy of SLT in people of African descent with glaucoma

It's interesting. SLT is based on the concept of selective thermolysis. That's where the selective in selective laser trabeculoplasty comes from

Selective thermolysis basically means that the configuration of the laser parameters is such that the laser energy is absorbed only by the pigmented meshwork cells, not by the nonpigmented meshwork cells

And the duration of the laser pulse, three nanoseconds, is short enough that there is no collateral thermal damage to those nonpigmented cells that don't absorb the laser energy

This is relevant because pigmentation patterns in people of African descent are different from Caucasians. And so, it's not inconceivable that the absorption of laser would differ in those two populations

And therefore, the safety and efficacy profiles of SLT may differ in Caucasian and African-American eyes. That was one of the impetuses for this particular study

So, our hypothesis was that SLT monotherapy can provide safe and effective control of IOP in glaucoma patients in the African-derived developing world

We've conducted a preliminary study with funding from the American Glaucoma Society

We enrolled patients who were St. Lucians of African descent, aged 40 or older, with primary open-angle glaucoma controlled on no more than one medication

Because we weren't sure how effective SLT would be, we excluded the patients with advanced glaucoma so that they would not get worse during the course of this study

For the purposes of the study, we defined advanced glaucoma as a large cup-disk ratio or central field loss

We hoped to enroll 30 patients in this preliminary study

All of our patients were washed out of their IOP-lowering therapy for a month, after which we measured baseline IOP twice one hour apart to get a good baseline established

Patients then underwent 360-degree SLT in both eyes in one sitting. We reexamined them one hour, one week, and then one, three, six, nine, and 12 months after treatment

We have extended the study now through a second year of follow up. But, I'm only going to present 12-month data here

All of the IOP measurements with a mean of two Perkins values per eye, all of those IOP measurements were taken by the same examiner using the same tonometer, the methodology for which was turn the dial to 10, measure the pressure, turn the dial back to 10, measure the pressure again

All patients were assessed at the same time of day at every visit to minimize any diurnal IOP variability

We screened 82 potential patients for this study, hoping to find 30 who would qualify. We actually found 64 who met initial eligibility criteria. And we didn't have the heart to turn any of them away. So, we washed out 64

When we came back a month later, 61 of them still met eligibility criteria. Others had ended up with pressures that were too high after wash out and so were not eligible

Our definition of success was relatively modest. We hoped for at least a 10 percent reduction in IOP from pre-SLT washout baseline

This may seem very modest to some. But, keep in mind that we assumed that, A, patients were probably using beta blocker therapy predominantly. And beta blockers have a known tachyphylaxis issue with long-term use. So, we weren't really sure how much their pressures were going to go up when we washed them out

And number two, we weren't sure what the compliance rates were going to be either

So, again, we weren't sure what pressures were going to be like when we washed them out

Our overall goal was to demonstrate that SLT was approximately as effective as medications in this population. So, our goal was really to have IOP come down after laser by the same amount that medicines had lowered pressure

And we set the definition of success relatively modestly at 10 percent

If at any postoperative period the pressure didn't meet this success criterion, we would repeat the assessment within 48 hours

And if they were a failure at both of those time points, then they were either restarted on medications or offered SLT retreatment

We only offered retreatment if the initial SLT provided them at least six months of benefit before it wore off. Anything less than that, and it wouldn't have been practical to repeat

Let me share our results with you. Of the 61 patients who underwent bilateral SLT, 58 of them were available to be seen at the 12-month mark. Two were off island, and one had died of unrelated causes

But, all 60 of the surviving 61 were still actively in follow up. We had a 100 percent follow-up rate through 12 months, by which I mean that the two who were off island at 12 months were seen at the next visit at 15 months

Looking at the demographics, all of our patients were African derived. The average age was in the low 60s

Approximately two-thirds were female. These are very similar to virtually every glaucoma study done in the developed or developing world

Corneal thicknesses were a little then at 535. And the cup-disk ratio was 0.61 on average

When we met them on medications, the pressure in the right and left eyes were about 17.3, 17.5 millimeters of mercury

And as expected, about two-thirds of them were on a beta blocker, and a third were on a prostaglandin. Nine percent were on either something else or nothing at all

After a 30-day washout period, pressure went up to about 21, 21 and a half. That was about a 15 to 19 percent rise in IOP after washout

So, that was what medications were responsible, about a 15 to 19 percent IOP reduction

This is our laser data, showing that we put in approximately 105 shots in each eye. The laser total power was a little higher in the left than the right eye

A word on our endpoint, we actively titrated the power throughout each procedure, looking for the little tiny champagne bubbles that have been described as the ideal endpoint

We didn't want to see tissue blanching. So, we adjusted the power throughout each procedure so that every two or three shots provided champagne bubbles

This slide shows our IOP response profile through 12 months. And as you can see going from left to right, we started out at about 17, 17 and a half on medications, washed out around 21, 21 and a half

By one week post-SLT, we were already below the treated baseline and well below the untreated baseline

And by one month, the full effect of SLT was evident with average pressure reductions running around 13, 13 and a half. And this was consistent and maintained in both eyes through 12 months of follow up

The number of subjects contributing data to this slide is given in parentheses under each time point on the X axis

Because people underwent retreatment or reinitiation of medications, they were removed from the analysis once they reached a failure endpoint

The high pressure that prompted them to be deemed a failure is included in this data. All subsequent pressure measurements are not

This is the Kaplan-Meier survival curve looking at a 10 percent reduction from baseline as the success criterion

And as you can see, through 12 months of follow up, there's about a 75 percent success rate. Seventy-five percent of patients are still enjoying a 10 percent or greater IOP reduction from baseline

If we make the success criterion more stringent and look at, at least a 20 percent reduction from baseline, our 12-month data still shows that approximately two-thirds of patients are a success at the one-year mark with 20 percent reduction being the definition of success

I think a responder analysis probably describes this data most effectively

If we look at the 46 subjects who were still controlled at 12 months, this is--they've undergone SLT in both eyes. And both eyes are still meeting the minimum 10 percent IOP reduction criterion at 12 months on no medications with no subsequent interventions

Naturally, by definition, all of them are meeting the minimum 10 percent IOP reduction threshold

But, let's look at the rest of it here. Ninety percent of patients at 12 months enjoyed a minimum 20 percent IOP reduction in both eyes

Two-thirds of patients enjoyed a minimum 30 percent IOP reduction in both eyes at 12 months

Half of patients had a 40 percent or greater IOP reduction in 12 months after a single session of SLT in both eyes

And a not insignificant proportion had IOP reductions exceeding 50 percent in both eyes 12 months after SLT therapy

These numbers may seem far fetched. But, in fact, they benchmark to other SLT monotherapy studies fairly well

This was a study by Nagar et al. published in 2005. And as you can see, the yellow bars showing what their study found are very similar to our 20 and 30 percent responders in our study

Also, McIlraith did a similar study. And again, the numbers are very similar to ours

So, I think that our data are supported by previous studies and perhaps are a little bit more illuminating on the high end in terms of 40 and 50 percent IOP reductions and in a population that hasn't been studied before

In terms of safety, almost every patient had a brief but intense period of photophobia that came on during the second day and lasted through the fourth or fifth day postoperatively

Only one patient called and required evaluation. And we ended up prescribing an NSAID for three days

I suspect this was related to anterior chamber inflammation. We did not use any prophylactic anti-inflammatory therapy postoperatively in these eyes

In addition, five eyes of three subjects had an IOP spike that exceeded five millimeters of mercury. But, none of these exceeded 10 millimeters. And all of them resolved without treatment by one week

Similarly, the photophobia had resolved in all patients by one week as well

From these data, we can conclude that SLT can be safely performed in eyes of people of African descent. The therapy lowers IOP by an amount that would reasonably be expected to alter the natural history of glaucoma in this population

Our results are consistent with previous studies of SLT monotherapy. And also, with the finding from the advanced glaucoma intervention study that people of African descent respond well to trabeculoplasty

And I think it's really important to point out that most of the treated patients enjoyed a very large IOP reduction without the need for medications at least 12 months after treatment

In terms of practical applications, this preliminary data supports the potential role of SLT in altering the rate of blindness due to glaucoma that is seen in the African-derived developing world

We still have some work to do. This 12-month data is impressive and encouraging. But, we still need to characterize the long-term IOP profile of SLT in this population. We still don't know how long it lasts

We don't even know the median survival time of SLT because we haven't gotten to a point yet where half of the patients have failed

Once they do, we need to evaluate the repeatability of SLT in this population

We also need to confirm the generalizability of the results we're getting in St. Lucia to--in a similar population but an independent one

Our plan is to repeat this study in a neighboring island to ensure that the results we're seeing are typical of people of African descent throughout the world rather than just St. Lucians in specific

The long-term goal is to establish a pan-Caribbean glaucoma laser program that will allow us to reduce or prevent glaucoma-related blindness in this region that is underserved and overburdened with glaucoma

I have to acknowledge my team and my partners. We've had, as I said, support from the American Glaucoma Society. Lumenis provided the laser that we've been using

We've also had funding and in-kind support from other agencies and entities. And we've enjoyed the support and collaboration of the St. Lucia Blind Welfare Association, the S. Lucian Ministry of Health, and the entire eye care community in St. Lucia

Thank you very much