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DR. DAVID HUANG: I've been involved with OCT for a long time since the beginning when I was working in Professor Fujimoto's laboratory in the initial development of OCT. And then a few years later Joe Isait [phonetic] who was a post doc in Professor Fujimoto's laboratory then spearheaded a project that produced the first corneal OCT images. And I was also involved in that and that was published in 1994 and when I got my first real job in Cleveland Clinic I was happy to find that Joe Isait [phonetic] was actually right down the street at Case Western so we got together and developed a high speed time domain in -- and OCT and that evolved in the Visante and it was really useful for a lot of things.

But the next step is to have higher speed and finer resolution like the ex-NASA administrators say, you want to do things faster, better and cheaper, but he never was able to accomplish all three in any single project. But amazingly I think we've done it in terms of the RTVue. So Fourier versus time domain, two different technologies. The Visante is actually pretty amazingly fast for a time domain system, but you can see it's really pushing the envelope at 2,000 axial scans per second. The RTVue is able to achieve 26,000 scans per second because it uses a different detection system, the Fourier domain system, and it also uses shorter wavelength so--and a wide, broader bandwidth so resolution is better. And the speed difference is ratio is still actually similar to that between a jet airliner and an original biplane.

And RTVue is a Fourier domain OCT system that can be used for both retinal imaging and corneal imaging, so it's very attractive in some practices that involve both. And it accomplishes that with a corneal adapter. The higher resolution has advantages in being able to see very detailed structures so in a Visante image you can see the - - here and sometimes a Bowman peak, but with the FD-OCT you can see the Bowman actually have two peaks, front and back. And of course you can see the endothelial peak. In the image this is really amazing. It's--you can now see the epithelial thickness of course and the Bowman's layer is kind of a double layer like a railroad track, front and back and you can see - - membrane and the endothelium and of course LASIK flap is easier to pick out because of the higher resolution.

If you are a glaucoma specialist you're interested in the angle and you can see things that you couldn't see before with lower resolution, such as the Schlemm's canal, the trabecular-meshwork. You can see the endothelium so you can trace it to see where it stopped and that's Schwalbe's line and that corresponds to the external limbus where you can see the transition from the corneal epithelium to the conjunct - - epithelium which looks different in transparency and thickness.

The higher speed is mainly an advantage in mapping. Now we can perform eight meridional scans in a small fraction of a second and of course you can produce a thickness map and we've done studies to show that the thickness map is almost five times better in terms of the rule mean square precision of the map compared to the slower Visante. The topography map is also a lot more accurate. And in terms of corneal power measurement the Visante was barely adequate at 0.8 diopter repeatability, but the RTVue is about three times better at 0.26 and now that is comparable to the best topography and keratometry systems. So it's about the same as keratometry but it measures both front and back which is a very significant difference that I will talk about later.

So I'm going to talk about different applications. First I think the RTVue with a corneal adapter module is going to be useful for corneal specialists who are involved in cleaning the front window of the eye. This is a desect [phonetic] case where the surgeon was a little confounded first day post-op because of some surface opacity here that wasn’t--that didn't allow him to see the graft very well. And he thought it was awfully close to the iris and so may have been detached. So he got his OCT and found that in fact the graft was very well attached but there's anterior peripheral synechia, that closer angle there like in this optical illusion.

This is a case of anterior lamella kerotoplasty and OCT is useful at looking how deep the dissection is and also how well the edges match.

I often use OCT to see if a patient is a candidate for PTK or not. In this case it's obviously not because the scar is close to full thickness here and even where there's partial thickness there's very little clear stroma left. On the other hand in this case you can see that most of the opacities are between 60 to 160 microns in depth and there's plenty of cornea between 570 to 600, so this is a case that would be amenable to PTK.

This is a case of Reis-Bucklers' Dystrophy and you can see this kind of washboard stromal surface that's smoothed out by the epithelium. This corresponds to the kind of reticular appearance on stroma examination. So the opacity is pretty deep here, 200 microns, but the cornea is also very thick so a trans-epithelial ablation here would help and actually did help.

Sometimes if you export the data; I've done this, too. One thing that's helpful is to simulate a PTK by taking off a fixed amount of tissue from the epithelial surface and here you can see that just by taking off the epithelium you really reduce a lot of the irregularity on the stroma surface. And here is the stroma surface. And by the time you got to 100 microns you removed most of the opacity and you might stop at 120 because you don’t have to remove the entire opacity if you have concern with high peroptic [phonetic] shift. So this is a great tool for planning.

I think the RTVue is also useful for the LASIK surgeon, first in looking at the flap thicknes. We're concerned with flap thickness because we want to preserve the amount of tissue under it so you want to see how deep your micro-keratome is cutting. The RTVue provides the A Meridians in the corneal scan so you can measure the flap thickness on all these meridians if you'd like to. Another feature that's very useful, especially for longer post-operative period is there is frame averaging so that you can pick out the interface better now without the interference from spackles.

Another thing we are really concerned about in screening LASIK patient is to detect early keratoconus and topography is a really valuable tool and I think the OCT pachymetry map might be helpful as well. We've done a fairly systematic study for, of keratoconus and we found that the useful parameters are the asymmetry of the thickness between the inferior and superior octans [phonetic] inferior temporal and supra-nasal octans [phonetic]. And you have to remember that a threshold of minus 45 microns. Also the cornea is thinner than 470 is suspicious or if the minimum minus maximum is more than 100 microns difference, you'll be suspicious for focal thinning.

And this is an example where every single one of these criteria are met so this is a fairly clear keratoconus of course. But even if you have one parameter you should be suspicious and if you have two parameters that's abnormal. That's pretty good for a diagnosis. So again, this case the asymmetry between the quadrant down here is supra--inferior--temporally and supra-nasally was beyond 100 microns so certainly way beyond the 45 micron cut off and the minimum thickness is 404, much thinner than 470 and the focal thinning minimum minus the maximum was 142, much less than minus 100.

It's also useful for refractive surgeons who perform a thachay [phonetic] intraocular lens implants. In this one example you can see there's good clearance of the ICO over the lens.

And I predict that RTVue will also be useful for the cataract surgeon who has refractive cases, which is very common. We know that intraocular lens power calculation is problematic after laser vision correction in virgin eyes. Usually we can--90% of the time we can get the outcome to be within one diametral ametropia if that's the target. In post-LASIK eyes that's much less frequently achieved and these are just a patient who cannot tolerate going back to glasses because they paid--they probably paid you $4,000 or $5,000 to get rid of them in the first place. So this is even a bigger problem than it might appear.

And this is still a growing and unsolved in 2006. Dot Koch [phonetic] was the editor of JCRS at that resolution of this problem to require a method for accurately measuring the posterior corneal power and now I will show you why that is. The problem with IRL calculation is that of keratometry. When you do keratometry you basically measure the slope at a ring, at the ring projection, and that's really two points on a cross section and then you extrapolate that into the whole anterior surface, and posterior surface. Now in a virgin eye the surfaces are very regular so this is a pretty good extrapolation but in a post-LASIK eye it doesn't work. The anterior surface is not uniform and forget about correlation with the posterior surface; that could be really way off.

So with OCT though we can directly see both a front and back surface and what we've done is to measure the curvature of the anterior and posterior surfaces over a 3 millimeter diameter area and then use that to calculate the power. So we take the measurement over eight meridians. The scan is actually bigger than what we need, it's a 6 millimeter scan. What we do then is we perform segmentation from this image to get the front and back boundaries for every meridian. We do a parabolic fit over a central 3 millimeter to get the average curvature for each meridian, and then we calculate the power of the front and back surfaces. And then we average the A meridians--we actually do, capture--every time we scan we capture three consecutive sets so we average the three sets. And we tested this on a small set of eyes, 14 normal, nine post-LASIK and six keratoconus eyes and each eye was scanned four times, that's four times three sets at each session. But it goes very fast because it scans it--this system is very fast. And what we found is pretty much what we expected. Some notable things are that in post-LASIK eyes the posterior cornea was not more curved than the normal, in fact, it was slightly flatter. This is different from ORB scan where you can see sometimes you see increased posterior elevation. So we didn't find that we have destabilized the cornea in all in this group, so I tend to believe that ORB scan finding is an artifact due to a low resolution. With a high resolution here you don't see that.

And in keratoconus eyes you see anterior increasing curvature and posterior increasing curvature so this should also help us detect keratoconus when you put it together with the other information. And the reproducibility for cornea power measurement now is very good, both in normal eyes and post-LASIK eyes. So we should be able to use this value to calculate IRL power that you want post-LASIK.

With keratoconus it does affect our accuracy because the cornea is more irregular.

This is a Bland Almond [phonetic] analysis of the normal group using the algorithm we developed in house and the agreement is pretty good. The OCT-derived corneal power was a little bit higher than ORB scan, a little bit lower than IRL master, so the truth is somewhere in between. We probably have it. And if you look at the scatter though, the agreement is just fair, so there is slight disagreement between these systems and because we don't know which one is gold standard I cannot say how accurate it is.

Optovue has already ported the corneal power algorithm. It's based on the same principle but we are now taking even more scans; we take five consecutive sets of corneal scans and then the algorithm chooses the best three out of five to average. And the results are similar. We have a set of 21 normal eyes of 12 subjects. Repeatability is 0.28 diopters and again, there is a little bit of disagreement with the ORB scan and the average is slightly higher. Now really to see which system is more accurate we need an independent correlation and what we are doing is we are actually studying the accuracy of refractive outcome based on IRL formulas using, you know, ORB scan, OCT and IRL master in a prospective trial of IRL, of cataract surgery IRL power calculation in both post-LASIK and normal eyes.

Finally I will want to talk about the useful of the RTVue for the glaucoma specialist, not in the neo-ophthalmology role but in the plumbing role where you're looking at the plumbing of the interior eye and this is an angle drawing from histology. So you can see that - - spread actually come up into the trabecular-meshwork and trabecular-meshwork gets pretty long. It goes from Schwalbe's line even a little bit posterior to the scleral spur and the Schlemm's canal is kind of in the posterior portion of the whole trabecular structure.

And I'm going to have you remember that and look at these OCT images, so again, what I do is I go to the external limbus and then come down and I actually see the termination of the endothelium, so that's Schwalbe's line. And a useful measurement there would be to look at the angle opening distance here at a Schwalbe's line. I think it's better than the old approach for ultrasound and Visante where you try to look for the scleral spur which is not that well defined. This is probably a better direct measurement of angle opening. And then you can see the trabecular-meshwork is this low intermediate reflectivity structure. Sometimes you can see a Schlemm's canal and this would be where the scleral spur is so you can see the scleral common here and there's an interruption here.

This is a narrow angle and this particular case the Schlemm's canal is even more clear and the scleral spur is even more clear and you can see the trabecular-meshwork going up. You can see a little bit better here probably because sclera is thinner in this case; that's why I picked that case actually. And you can see the Scwalbe's line very clearly. And this case there's a synechial angle closer due to neovascular glaucoma. You can see these thick vessels which is abnormal and then there's PAS that closes that angle and the Schwalbe's line is here. So many landmarks that are useful for diagnosis of different kinds of angle closure. This is after trabectome surgery where you see a cleft where the trabecular-meshwork would be. This is residual remnant of the trabecular-meshwork.

So that's all the material I have. I want to thank Optovue and National Eye Institute for supporting our research and I want to thank the people in my research team. We call it the Center for Ophthalmic Optics and Laser, standing for COOL, and we're at the Doheny Eye Institute. Thank you.