The Optic Nerve Head

Evaluation of optic disc and nerve fiber layer in glaucoma

Clinical techniques

Joseph Caprioli

Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA

This is a review of the clinical evaluation of the optic nerve and nerve fiber layer. Figure 1 shows a pair of optic nerve photos from a 40-year-old patient. He is a bricklayer and he has had pressures in the right eye in the mid-thirties and pressures in the left in the mid-twenties for some years. Despite acquired cupping in the right eye, this patient’s visual fields remain normal in both eyes. The next example is of a different patient, the same eye imaged over a two-year interval (Fig. 2). Let me draw your attention to the inferotemporal rim and I think you will see that there has been a significant change there, a notch developed with thinning of the neural rim, and you can look at this vessel and see how this vessel has dipped into that notch. The vessels will give you clues as to where to look for changes in the neural rim. Despite this progressive change over that two-year period, this patient’s visual fields remain normal, at least to standard automated perimetry with white stimuli and a white background. These examples demonstrate how the visual field and disc can progress over time in some patients with glaucoma.

In general, we first detect structural change up to some threshold, at which point our psychophysical functional measurements become abnormal. As the disease progresses, both the functional and structural abnormalities tend to get worse. Later in the disease, there may not be much left of the disc (Fig. 3). The disc can be pretty bad, almost totally cupped, and we can see continued changes over time in the visual field as the patient gets worse. Early on in glaucoma, it makes sense to pay particular attention to the structural characteristics of the eye, the disc and the nerve fiber layer, and later on in the disease, to follow functional tests as a more sensitive measure of progression. We are going to focus on this early part of the disease and on different ways of evaluating structural characteristics of the nerve.

The direct ophthalmoscope is sometimes useful when you have patients with miotic fixed pupils, but whenever I want to have a good look at a nerve, I dilate the eye and perform a good stereoscopic examination using a hand-held lens at the slit lamp, in addition to disc photographs. The worst way to look at a disc is with

Address for correspondence: Joseph Caprioli, MD, Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Suite 2-118, Los Angeles, CA 90095, USA. e-mail: caprioli@ucla.edu

Glaucoma in the New Millennium, pp. 107–114

Proceedings of the 50th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, April 6-8, 2001

edited by Jonathan Nussdorf

© 2003 Kugler Publications, The Hague, The Netherlands

Fig. 1.

Fig. 2.

Fig. 3.

an indirect ophthalmoscope. Discs usually look better than they really are with an indirect. The disc is small and has better color when you use an indirect ophthalmoscope, and I think this is because you are illuminating a large portion of the surrounding choroid and the ‘redness’ bleeds into the disc.

Fig. 4.

Particularly in the early stages of glaucoma when you are looking for early or small structural changes, it is mandatory to use a magnified stereoscopic view at the slit lamp. Cup-to-disc ratio estimates are not sensitive or specific indicators for the presence or progression of glaucoma. We may think that, “Well, if I’m looking at this disc every time once a year and I’m making the same estimate, then I’m pretty good at these estimates and I can detect small changes.” It has been shown that we are quite variable in our estimates, even those of us who do this for a living. Finally, in clinics where there may be different doctors, particularly in a fellow or resident clinic where there may be different practitioners seeing the same patient over time, cup-to-disc ratios are useless and counter-productive.

Photographs are the best way to document the appearance of the optic nerve. Second best would be careful drawings; a drawing is much better than a cup-to- disc ratio estimate because you can show where the neural rim may be thin, where there may be a disc hemorrhage, where there may be some undermining of the edge of the disc, where the lamina is there, etc. (Fig. 4). So, drawings are second best to photographs.

The best sign of glaucomatous damage is progressive loss of the disc rim. In Figure 5 a few examples of progression are shown which I think we should all be able to detect in our practices. There is sometimes a sentinel vessel sign, and if you go back and examine the rim on the right, you will see that a new notch has developed between 6:00 and 7:00, and that this vessel has fallen into that notch, and that there is a real change for the worse. You would not be able to pick this up with a cup-to-disc ratio estimate.

In the next example, the neural rim in follow-up has become much thinner and in this area the disc is cupped right to the edge (Fig. 6). This is a real change which I think is clinically significant and one that we should detect. A very careful drawing might detect this change. A cup-to-disc ratio estimate by the best of us would probably not suggest a change, but clearly a comparison of photographs will show it very nicely.

Fig. 5.

Fig. 6.

Next is an example of a patient with a disc hemorrhage with follow-up showing some progressive loss of the neural rim in the same area (Fig. 7). This loss of the neural rim is not huge, it is fairly subtle, and if this disc hemorrhage was not here, perhaps we would not even pick it up. You certainly would not pick it up without the use of photographs. I usually get photographs at baseline and occasionally during the course of caring for the patient. I do not think you need to get them every six months and maybe not even every year, but comparing your examination to the photograph is certainly better than not having a photograph at baseline. I think you can pick up small changes if you are comparing photographs with photographs. I recommend, particularly in patients you might be concerned about, getting sequential photographs.

Disc asymmetry is a very useful sign. Of course, disc asymmetry does not have to be present in order to have glaucoma, but glaucoma is often asymmetrical, and you will see differences between left and right eyes. One little caveat is that if you are going to compare the appearance between left and right eyes, the size of the disc should be the same in both eyes since larger discs will typically have larger cups (Fig. 8). If you have a situation in which the two eyes have different-sized discs, which is rather unusual but certainly happens, then your evaluation of disc asymmetry should take this into account.

Fig. 7.

Fig. 8.

Disc hemorrhages only occur where there is nerve tissue left to bleed. Disc hemorrhages will not occur at a sharp edge of the scleral canal where all neural tissue has been lost. There is nothing there to bleed, but right next to that area, where there is presumably ongoing damage and some neural tissue being fed by vessels, there can be breakdown of the vessels and a disc hemorrhage can occur (Fig. 9). We know that the presence of a disc hemorrhage is a sign of poor prognosis. Individuals with disc hemorrhages are more likely to progress over the next few years than those without, and this has been shown in a number of studies.

Peripapillary atrophy is another non-specific sign of glaucomatous damage. This kind of atrophy is the irregular area of hyperand hypo-pigmentation. Peripapillary atrophy tends to be greatest where the neural rim is thinnest (Fig. 10). Whether this is a precursor of neural damage to the disc or a consequence thereof, we really do not know; in a prognostic sense, it may be similar to a disc hemorrhage. There

Fig. 9.

Fig. 10.

is a correlation between progressive peripapillary atrophy and progressive disc damage. In a study we conducted a couple of years ago, we were able to show that progressive enlargement of peripapillary atrophy was correlated with progressive disc and field damage. There is a loose correlation between loss of the neural rim and enlargement in this area of peripapillary atrophy, but we cannot say anything about cause and effect.

Another sign of glaucomatous damage which I am interested in is so-called ‘focal ischemic glaucoma’. Spaeth was the first to coin this term, which describes a very focal change in the optic nerve, which I would consider a subset of a notch. It is probably a form of a notch, but it is slightly different in that it occurs very focally, either at the slightly temporal inferior pole of the disc or at the superior, slightly temporal pole of the disc. It can be very deep, so if you imagine that this neural tissue is made of soft butter and you stick your finger straight into it and take it out, this is what would be left, this very focal deep, for lack of a better word,

Fig. 11.

pit (Fig. 11). It should not be confused with a congenital pit, but is rather an acquired pit from glaucoma. A true acquired pit is separated from the central cup by some intervening tissue which differentiates it from a notch. At the bottom of this pit, the lamina cribosa looks altered and has a grayish appearance, and the laminar pores may be stretched and large. The pit has peculiar characteristics and it has been described by various names. The use of the word ischemic is, I think, unfortunate. We have no idea whether or not it is ischemic in nature, but it is similar to the presence of a disc hemorrhage, in that we were able to show that the presence of a pit is a poor prognostic factor. We match patients for the stage of glaucoma, pressures, and other variables, except for the presence or absence of an acquired pit. Those with acquired pits had a much higher rate of disc and visual field progression over a five-year period than those without.1 We think that this is probably a sign of progressive damage, and it may very well be an indicator of poor prognosis.

A frequently asked question is, “Should I examine the nerve fiber layer in glaucoma and, if I do, how should I do it?” There are diffuse and localized types of nerve fiber layer loss. In Figure 12, we can see large wedge-shaped defects both superiorly and inferiorly which we would classify as a focal type of defect. In addition, there is probably diffuse nerve fiber loss throughout as well, which is harder to call in the early stages, but is probably more specific when it is more advanced. You can detect nerve fiber layer loss with dilated direct ophthalmoscopy and a red-free light. The easiest way to detect nerve fiber layer loss is to take photographs utilizing a special narrow-band filter in your camera and a highcontrast film and development process.

Figure 13 is an example of a patient with no glaucoma in the right eye, angle recession glaucoma in the left eye, and diffuse nerve fiber loss in the affected eye. The thin striations that can be seen in these bundles in the normal eye are really quite normal. Defects should be wedge-shaped and point to the disc. In the left eye, rather diffuse severe loss can be seen, which is fairly extensive. The striations that are normally there are lost. The fundus looks a little bland because the structure from the internal retina is missing, and the small vessels actually stand out in

Fig. 12.

Fig. 13.

relief because they are now more visible. They are not buried by the nerve fiber layer. In younger patients, glaucoma suspects, ocular hypertensives, or if the disc does not quite look normal and we really need better evidence to say that it may be abnormal, I would look for nerve fiber layer loss. I pick and choose patients to do a careful nerve fiber layer examination.

Careful structural evaluation of the optic nerve and nerve fiber layer is an important diagnostic step and should be performed in all patients suspected of having early glaucomatous damage.

References

1.Ugurlu S, Weitzman M, Nduaguba C, Caprioli J: Acquired pit of the optic nerve: a risk factor for glaucoma. Am J Ophthalmol 125:457-464, 1998

Round table

How I follow the optic nerve head and nerve fiber layer: my step by step approach

Claude F. Burgoyne, MD, presiding

Panel: Joseph Caprioli, MD

George A. (Jack) Cioffi, MD

Harry A. Quigley, MD

Dr Caprioli: We have a round table discussion on how I follow the optic nerve and nerve fiber layer, and there may be some diversity of opinions here, and I think that would be useful to explore. After this session, we will have a question and answer session.

Dr Quigley: Looking at the nerve fiber layer for me is something I do more often because it is something we began doing a long time ago and did a bunch of studies on, and it’s free. You are looking at the stereo appearance of the optic disc in white light, and all you have to do on your slit lamp is to flick a green filter in and look. The situations in which it is really helpful include the discs where you are looking at somebody with a 0.6 cup bilaterally. The question is, is that a physiological cup or is it early glaucoma? If there is nerve fiber atrophy, it would really swing you in favor of either following the patient more closely or starting treatment on someone if they had normal fields. If they have a field defect, obviously you don’t necessarily need the nerve fiber layer, except as confirmation that it is not a phoney field, and there are people who have a field defect that goes away with practice. The second is an asymmetric case where you have a 0.7 cup on one side and 0.4 on the other. That is beyond the population frequency of asymmetry, enough that you would say, “Boy, 0.7 and 0.4”. Could somebody have that physiologically? They could, but if the nerve fiber layer is poorly seen on the side of the 0.7 cup and beautifully seen on the 0.4 side, you have just had confirmation that there is early damage in one eye. If nerve fiber loss corresponds to the field defect, and that is also where the notch is, again, it is a situation where it is helpful. The question is, how do you do it? How do you look at it? For some years, I tried to teach this in lectures showing people, and everybody said, “Yes, the pictures are kind of pretty, but I went home and tried to do it in the office and I couldn’t”. So I wrote a book on the subject. The book sold out. Nobody seems to be doing it. So, I am glad there are machines that are now doing it, or at least attempting to, because I think it will help you.

Glaucoma in the New Millennium, pp. 115–128

Proceedings of the 50th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, April 6-8, 2001

edited by Jonathan Nussdorf

© 2003 Kugler Publications, The Hague, The Netherlands

Dr Caprioli: Jack, your view on where the nerve fiber layer exam fits in to your practice.

Dr Cioffi: I think it fits in even more often perhaps than Harry suggested. I examine the nerve fiber layer in virtually all patients, because it is one more clue about progression. I don’t take photographs of the nerve fiber layer because we don’t have a photographer who really gets reliable, reproducible photos to the extent that Harry has been able to do. As he said, it’s free. You are sitting there. All it takes is to flick the light over to green, and you can do it on virtually any patient. His examples are right on, but I think that in any patient in whom you are questioning progression, you can add it to the drawing of the optic nerve as you are taking notes. It is hard to get reproducible numbers, just as Joe mentioned, with the cup-to-disc ratio without having the photographs, but you can get an idea. And certainly the presence or absence of a new wedge defect you can recognize if you look each time. So, I would urge you to do it more often than not, and even if you can’t take the photographs, the beautiful photographs that we are showing, you have the green light on your slit lamp.

Dr Quigley: In trying to teach it, we found that one of the ways you can learn to do it yourself is to look at eyes in which the patient has definite damage in one eye and has a normal eye on the other side. This lets you try to see some of the things that were being illustrated here, that there is a dense pattern in the normal – but it looks like a mat finish when they are not there. The blood vessels are very clearly seen when the nerve fiber layer is gone, because they are not buried in nerve fibers. So, when somebody has bad field loss on one side and a normal eye on the other, do try to look at the nerve fiber layer in both eyes. What you will see is the normal pattern in the left eye and what atrophy looks like on the other side, live. As we have tried to evaluate in studies, the photographs are extremely helpful, and in fact you can see the pattern much better in pictures than you can clinically. I don’t mean to say that it is an easy thing to do, and the photographs do help. The problem with the photographs is that you have to dial the Zeiss flash fundus camera up to flash 6, and it is really bright and patients don’t like it and that’s why they like the GDx Nerve Fiber Analyzer (GDx, scanning laser polarimetry) and Heidelberg Retina Tomography (HRT, confocal scanning laser tomography). The laser images don’t have a big flash.

Dr Caprioli: Claude, do you have anything to add to that? How do you mesh those two techniques, optic nerve and nerve fiber layer exams?

Dr Burgoyne: Joe is asking me a tough question. Having trained with Harry, I got wonderful experience with the nerve fiber layer, and at LSU we had a hard time getting consistent photographs. However, clinically, I use it to confirm nerve fiber layer loss in patients in whom I am confused by the appearance, and in addition to the ways that have been outlined, I believe that sometimes you have change in the rim or loss of nerve fiber layer that isn’t associated with change in the rim. You might look for pallor, but nerve fiber layer dropout can occur before the pallor, and I use it in that situation as well, in addition, of course, to the others that have been outlined.

Dr Caprioli: To get an idea about how important you think it is, if you took, let’s say, 100 patients with glaucomatous damage, let’s leave it at that, a fairly broad category of patients, and you’ve done a careful optic nerve exam and a careful nerve fiber layer exam, and you have the field in front of you, in how many of those 100 would you think that adding the nerve fiber layer exam really added to your ability to follow that patient over time or to detect something different that you didn’t detect in the nerve?

Dr Quigley: I read a paper once by Caprioli which said that the nerve fiber layer didn’t add much, although its information was almost as useful. Is that a summary of the manuscript?

Dr Caprioli: Yes.

Dr Quigley: So you could get the information from the nerve fiber layer, you could get it from the disc. There were some additive features that were good. We followed a group of 800 glaucoma suspects for 11 years and took pictures of all of them, and we looked as they went from no field loss to field loss, going back up to 5 years prior to the time that they developed their field loss. The idea was, which technique would best predict which person was going to get their first field defect. We looked at both color disc photos and at the nerve fiber layer pictures in a masked fashion, and were a little disappointed that the cup change was not detectable to us except in about 20 or 25% of eyes before there was field loss. They had suspicious discs. If you just looked at a basic disc, the basic disc was a 0.6, 0.7 cup, you would have been suspicious. That was a high level suspect. But the disc didn’t change as often as I would have thought. The nerve fiber layer changed 50% of the time before there was a field defect, in our readings of these ideal photographs that we are talking about. So, I think that instruments, or an experienced human who can detect the nerve fiber layer, can detect persons who are actually progressing to the early stage of initial white-on-white visual field loss.

Dr Cioffi: I think we are all saying the same thing. I just think it is one more piece of the pie. It gives you a little more confidence in the difficult patient. I don’t think most of us have the availability of photographs. I don’t think it is easy for patients or easy to get reproducible photographs, and so we have to rely on our clinical abilities, and I think it is worth adding, especially in the difficult nerve where you are up in the air with the asymmetry that Harry talked about, or the Clairol patient

– does she have glaucoma or doesn’t she? Those are the patients in whom it is most helpful.

Dr Caprioli: Let me just add one comment, if I may. And that is, we’re talking about these two exams as if we are looking at different things. We are looking at the same thing in two different places, of course. We are looking at the nerve fibers as they are crowded toward the disc, or we are looking at them once they are splayed out over the retina. The way I often think about it is that small, early defects, particularly if they are focal, can be lost in the mass of fibers once they have congregated at the disc, but if you take them and you spread them out over the surface of the retina, they are more often detected as a nerve fiber layer defect. So, my opinion is that, in early disease, you can substantially add to your detection rate of abnormalities by adding the nerve fiber layer exam, whereas later in the

disease, it is often not all that helpful. That is my view.

Dr Quigley: By the time there is moderate field loss, you can’t see the nerve fiber layer at all clinically. Ask yourself, when is the nerve fiber layer exam not helpful? By the time you have a mean defect of –10 dB in a Humphrey, the nerve fiber layer has gone, forget it and the disc is blown. Well, that is Joe’s point. By the time you are halfway into the damage pattern of glaucoma, which is really 75% of the way into the optic disc, you are on fields entirely.

Dr Caprioli: I would assume that every one of the panel members gets photographs of the optic nerve at least at baseline. Let’s say in a patient that we are going to continue to see in the future. Am I correct in that assumption? Yes. Now what I would like to know, and I think what the audience would like to know, is how do you use those baseline photographs? Do you examine the patient ever so often, sequentially compare your exam to those photographs? Do you re-photograph the patients? If so, how frequently do you do it and what kinds of patients do you do, and so forth? Claude, why don’t we start on this end with you.

Dr Burgoyne: Joe is being nice enough to include me in the discussions. We have a tradition here of the local presenter chairman staying out of the discussions, and I think maybe I’ll do just that... I know that Harry tends to be a bit of a junkyard dog and he is the kind of person you want on your side. I am actually glad you brought it up, Joe, because I feel strongly about photographs as opposed to the newer imaging modalities, which we are all excited about and which we hope will come into clinical practice. The one thing that we should all be doing is taking good photographs. I do it at baseline, and then I do it subsequently whenever I am concerned about change. Sometimes it is to confirm a change. Sometimes it is because the visual field has changed, I don’t see anything in the nerve and I want to know. Sometimes it is because, as Joe mentioned at the end of his talk, you just think it is about time to reassess, because there are two levels of variability in the assessment. First, you are looking at the optic nerve through the slit lamp through a dilated view, and it doesn’t correspond to the 2X photo. The views are different. Second, photos don’t correspond to one another, and so sometimes I get nervous and I’ll just get another set of photos and look and see how much variability is present in the photos, illumination, clarity, stereo, compared to the original ones. These are the ways I use photos, not on a routine basis, but when I feel I need them.

Dr Cioffi: I actually do very much the same as Claude. I get them at baseline for a couple of reason. One is for the baseline measurement so that I can look later. The other is that we have an HRT which we will touch on later, and I believe to draw the contour line on an HRT at baseline, you actually need a stereo disc photograph. You can’t draw without it because, if you are going to be consistent in getting the line at the scleral exit, then you have to have something to go by. Often the image on the HRT itself isn’t sufficient. We literally have thousands of patients in various studies, following them over long periods of time, and you can’t just draw those circles without it. So back to clinically, I get them at baseline. I don’t have a set pattern of when I get them. Similarly to what Claude just said, I get them when I am concerned about change. When I see something that alerts

me to look in an area more carefully. But what we never talk about is how we actually use them. What I do is – the technician who is working up the patient actually pulls out the disc photographs and, in my top drawer on my writing table is a light box in each room, and I pull out the light box and so that the photos are there ready for me when I walk into the room, it forces me to acknowledge them. I use them as I look at the patient. I will look at the photographs and then I will look at the patient and then I’ll go back to the photographs, sometimes three or four times even. I’ll say, “Sit back a second”, and I will look for a particular feature. I actually do use them quite intensely when I am looking at patients. It’s not all patients whose optic nerve you can get a look at every time you see them, but I make a point of getting a very good look, dilated if need be, at least once a year, as I am following the patient for the optic nerve. I try every time, but sometimes because of cataract you can’t, and I certainly don’t dilate patients on every threeor four-month visit. I use photos constantly, it is part of the routine in my clinic.

Dr Caprioli: Harry, do you do anything differently?

Dr Quigley: Yes, a little bit differently. I did a study in which I asked if I took pictures every year, so that I had annual photography, and then I played the game of only using the information from every fifth year, would I actually have decreased my ability to see change in these glaucoma patients? And the truth is that glaucoma moves slowly enough that we proved in that study to my satisfaction that, in most cases, I wouldn’t have lost a lot if I hadn’t done the photos every year. If you feel comfortable doing them every year and you think you might get information, you are probably giving Cadillac care. But the pictures are very uncomfortable and they are expensive. I am not sure that annual photography is something that I could justify. I take pictures every five years, and, as these gentleman said, I examine with a 90-diopter lens every single time the patient is in, which is typically twice a year. On one of those annual visits, they get dilated for the rest of their exam. The other time, you can use a 90 and look through most pupils very nicely. It was one of the nice things about the hand-held indirect lenses when they came into use. You are looking for a disc hemorrhage, or for some dramatic event that has happened in the back of the eye. Bear in mind that the clinical exam, as Claude said, doesn’t look like the photographs. Clinical stereophotographs do not have the depth of field that the live human does when you look at them at the slit lamp. Often you will look and you will say, “Oh my God, the disc looks much more cupped than in that photograph”. And you take some more photographs, then you lay the photographs side by side and darn it if they don’t look identical. The difference was the beautiful depth of field you get live on the human compared to the photo. So don’t be fooled by that particular aspect of it. I agree with the comment about the HRT. We have a technician who does the HRT exam, and then I look at the HRT and I compare it with what the patient looks like, and have the technician redraw the line so that the baseline HRT will more closely match the patient’s real disc.

Dr Cioffi: One other practical note is, in a busy clinic, if you are trying to take photographs more often and to judge your treatment on it, it becomes a bit of an issue because you don’t get the photographs back for a few days or a week, and

so you have to carve out a portion of time to actually look at them and compare them with the old photographs. It is reassuring to hear Harry’s one-to-five year jump, because I think it is true. On a practical note, I don’t know if you can do it much more often than that.

Dr Caprioli: If I may add two cents to this too. I think it is difficult to compare your exam to a photograph for the reason that Harry mentions. For that reason, I actually get serial photographs. The frequency is variable and I absolutely believe what Harry just said that one year is probably overdoing it. I probably do it every one or two or three years, depending on the patient, and I agree that that is probably overdoing it, but I think if you wait until you are suspicious on a clinical exam, you may already have missed something you could have picked up much earlier. For that reason, I tend to do them sequentially and to compare photographs over time. If you are going to do that, you have to make it easy on yourself, the practical aspect of it. What I do is to put the slides in these plastic sheets and organize them left and right stereo for the left eye, left and right stereo for the right eye, the oldest ones at the top, and then go down chronologically. You should have a light box in every examining room. You can rapidly compare those discs over time by using a magnifier or viewer and compare them one to the other. Unless I am particularly worried about someone, I don’t actually look at the photos until the patient comes back the next time, which may be after six months or a year. It sounds like I am not missing too much if Harry’s five year figure is right.

Dr Cioffi: If you are taking them every two years and they are not coming back for another six months to a year, you have really lost the benefit of taking them more often because there is another year delay before you evaluate the photo.

Dr Caprioli: I think there is some value to taking sequential photographs and I think the interval is up for grabs. Thank you very much for this round table discussion, gentleman, and I think Dr Burgoyne would like us to move into the question and answer session, so I will turn it over to him.

Question and Answer Session

Dr Burgoyne: I am sorry to have to move in this direction, and the only reason I pushed it was because we have a lot of questions and they are really good, and I think they will prompt a lot of interesting discussion. In routine glaucoma suspect patients, what screening visual field test are you using?

Dr Caprioli: Is this a patient with risk factors for glaucoma but a normal disc?

Dr Burgoyne: I think a glaucoma suspect. So let’s throw out the idea that they have no risk factors other than that their nerve is suspicious.

Dr Caprioli: First, we obtain a Humphrey 24-2 SITA-standard white-on-white. If that is normal, I would now generally add a blue-on-yellow to that, at least at baseline.

Dr Cioffi: That is exactly what I do. I may not add the short-wavelength at that visit. If I am suspicious enough then I am going to see them back in six months and if the white-on-white is totally clean, then I will just possibly do it at the next visit. It depends on my level of suspicion about the patient. When SITA (Swedish Interactive Threshold Algorithm) came out, we had to make a decision as to whether we were going to do SITA-standard or SITA-fast on everyone who came in. The decision in our glaucoma group was to use SITA-fast. We save two to three minutes per patient. We potentially lose some form of detectable glaucoma which is as yet unknown. Our patients are, in general, extremely happy with SITA, and I think it was a good decision on the part of Humphrey to go that way. We hardly use blue-on-yellow perimetry. The chief reasons for that are that it is arduous, extremely difficult, and in my opinion, the normative database is inadequate for representing the general population. As a result, nearly everyone has an abnormal blue-on-yellow field in some way or another. I think that, under ideal conditions, the blue-on-yellow test, in Chris Johnson’s prospective study, shows that the test is able to detect abnormality, and almost surely does so before white-on-white does, under the right conditions. But I don’t think we have a practical way of using SWAP (Short-Wavelength Automated Perimetry) yet, and until there is a SITA-SWAP and we have a better database for it, I am not going to be using it.

Dr Cioffi: I actually disagree on two points. The first is SITA-fast. I don’t think it buys you that much. These are generally younger patients, they take fields fairly quickly, and I am not willing to accept the increased variability on a patient on whom I am trying to pick up new disease for saving a minute per eye. I don’t think you save two or three minutes; I think it is less than that. I actually use SITAstandard and never SITA-fast. On the blue and yellow front, the normative database (I guess we were part of it so I like the normative database), especially in younger patients without cataracts, I don’t believe it is that difficult a test, and I don’t believe that the normative database is that insufficient. In fact, if you look at just the gray scale, all the gray scales look bad, but the pattern deviation plots don’t actually look bad. I think it is a valuable test. That said, we sorely need two things with SWAP. We need SITA-SWAP, and Humphrey has that message and I think they will develop that. It needs to be a quicker test, so it is easier. Another thing is we need is a Statpac type format where we can follow SWAP over time, and we don’t have that availability right now.

Dr Caprioli: I have become sufficiently comfortable with SWAP. Actually my initial opinion about this was much like Harry’s, but I have used it despite that to try to get some experience with it, and it is a very noisy test. There’s no question about that. But if you do have a patient whose abnormality exceeds the noise, and occasionally you have those with normal standard perimetry and a suspicious disc, that finding of a scotoma on SWAP can actually change the way I take care of the patient or the way I follow that patient. So, I think it is a useful addition in selected patients. My opinion about following for change over time with SWAP is that it is going to be very difficult, simply because of the huge noise and fluctuation of the test.

Dr Quigley: Just quickly, and Jack may want to comment again, when we said to Humphrey, “You are doing a standard algorithm test that is much too long and

what is happening is the patients get tired and you are getting unreliable information, make the test faster”, “Oh, my God, we can’t do that, it will change everything”. I think those of us who have been using SITA fields for some time, and I think Jack agrees with me, have realized that patients give more reliable answers and therefore, in a faster time you get a better answer. He and I can sit here and talk about which one we like, SITA-fast or SITA-standard. The truth is they are relatively close to each other. One is a little faster. I am opting for a slightly quicker test. He is hoping that, by spending a little more time, it is more reliable. You should do what you want.

Dr Burgoyne: Let me jump in and ask the next question. Do you consider the SITAstandard or SITA-fast test to be adequate for following glaucoma patients for progression? Since you have already said that you are using it, what is it you are using as criteria?

Dr Quigley: We have a real problem in that we have a situation where there is no new software being provided by the company, and the company will not allow us to get the data output in a usable computerized format from SITA-standard or SITA-fast. It has been encoded in a way that they won’t let us touch. This is particularly unfortunate because what we could do from our center in less than six months would be to provide you, through the Internet, with software that monitored progression in a variety of ways, and I would do it through free shareware. It is pretty clear that this is not going to happen anytime soon until we can crack what is coming out of the SITA data stream. Therefore, we are left sitting there laying them out on a table comparing them, almost as we were eight or nine years ago. Because you don’t have the kinds of regression comparisons and glaucoma change probability comparisons that we used to have. What you can do is look at the pattern standard deviation (PSD) and look for changes like the loss of a decibel per year. That in linear regression in the previous fields was a serious loss measure. So, a PSD, if it is going down by one or more per year, that is way beyond the standard that would occur in anyone of age, and is equivalent to what was going on, we hope, in the standard algorithm. The second is we look for individual points that have become statistically abnormal in the total deviation plot, particularly when it is the same point more than once in consecutive three fields, when it is a cluster of more than one point, but you are doing it manually, you are doing it by looking at it, and that is really pretty arduous. So I think we, at the moment, are stuck doing things like this. Maybe my colleagues have better ways.

Dr Caprioli: There is no statistical test that has been shown to be any better than just looking at a series of visual fields. The point-wise linear regression approach may turn out to be the best approach, setting some standards for minimum change, as well as statistical significance. But until that has been developed and has been tested in sort of a rigorous and longitudinal way, I think we are stuck with just evaluating fields over time. Just a couple of basic points about how to do that without getting into too much trouble. You need a large number of fields in order to deal with the noise of the test. You need to establish, at least in your mind, some magnitude of what the long-term fluctuation and of what the noise of the test is, and then you need to demand that any change you are going to call progressive

damage needs to exceed that magnitude of long-term fluctuation. This is how I actually evaluate fields over time and in a sort of qualitative semi-quantitative way. Until we get better and validate a statistical test, I am afraid we’re stuck with that approach.

Dr Burgoyne: What conditions other than glaucoma lead to nerve fiber layer loss, and how does the pattern of nerve fiber layer loss differ, for example, a disc drusen?

Dr Quigley: Anything that kills a ganglion cell is going to lead to nerve fiber loss. So, multiple sclerosis, brain tumors that affect the anterior visual pathway, ischemic optic neuropathy, they all lead to nerve fiber layer atrophy. They don’t lead to excavation of the optic disc, although they do lead to disc pallor. Now, the disc drusen can give you a disc change that looks like glaucoma, usually because it is a small disc and is full of drusen. Drusen can cause almost anything, and almost always confuse me as being something that could look like glaucoma. Not only in nerve fiber loss, but also in the visual field. They can be progressive as well. So, what you are left with, with a patient who has disc drusen, if they have a progressive disorder and you think it might also be glaucoma, is setting a very low target pressure. There are those who have been advocating lowering the eye pressure in eyes with disc drusen in whom you don’t have any reason to think the patient has glaucoma, but they are progressively getting worse, and it is something that I have offered to a number of patients, and that is what we have done in a couple of them. I have no idea whether it is beneficial.

Dr Cioffi: I’d say disc drusen, in particular, of all the ones that have been listed by you, are the most confusing, because they can produce almost anything, including an arcuate loss of nerve fiber layer bundle, and it can be difficult. But all the rest look different, especially based on the excavation.

Dr Caprioli: Can I tell you about an interesting case? This was a patient who had a diagnosis of glaucoma and her field looked a little glaucomatous, not quite typical, but there was some superior loss. If you used your imagination, it looked like a little bit of an arcuate pattern, some nasal loss, in both eyes, fairly symmetrical. She underwent LASIK and immediately after noticed a huge decrease in her vision, and her visual fields then tested like small tunnel fields, and she had extensive peripheral loss and small 5-10° central fields. When I finally got hold of her and examined her, it turned out she had disc drusen. She had small discs with disc drusen. I don’t think she had ever had glaucoma, but after LASIK, what I guess happened was with the high pressures and those little rocks sitting in the anterior optic nerve pressed against her nerve fibers and knocked them off.

Dr Burgoyne: In Ophthalmology this month is another first case report for a glauco- matous-like optic neuropathy occurring following LASIK.

Dr Cioffi: There are four refractive surgeons in the back row that just passed out.

Dr Burgoyne: Does the appearance of the nerve fiber layer differ with age and race, in your experience, or in the literature?

Dr Cioffi: I think the nerve fiber layer is easier to see in children and in darker pigmented fundi. It is just more evident on examination.

Dr Quigley: We lose some nerve fibers with age, so in addition to the fact that older persons like me are less pigmented in the posterior pole, you have a lighter background which makes it harder to see the nerve fiber there, you also have fewer nerve fibers. Our recent work suggested that nerve fiber loss, which is pretty modest through the first 50 years of life, accelerates between the ages of 50 and 90, so you are losing in the order of about 7000 fibers a year later on, so I am hoping for the best here.

Dr Caprioli: Also, I think in really young patients, you get this sheen off the internal limiting membrane which is a bit thicker, and it looks a little shiny. I think it sometimes makes the evaluation of the nerve fiber layer directly under it a little more difficult.

Dr Burgoyne: Do you start treatment in the glaucoma suspect with normal white- on-white fields but repeatable abnormal SWAP fields? How do you make that decision, Joe?

Dr Caprioli: I guess that would depend on how the nerve looked. I am not willing to put all my eggs in that one basket, that SWAP basket, without some corroborating information. If there was asymmetry that agreed with the SWAP, either within that optic nerve, it’s a superior versus inferior pole, or asymmetry compared to the other eye, and the other sort of social/medical factors favor treatment, age, and so forth, yes, I would consider treatment in that patient. But only if there were some corroborative structural damage as well.

Dr Cioffi: Yes, I think you have to put it, of course, as Joe mentioned, in the context of the patient. An 80-year-old with a SWAP defect and maybe suspicious nerves, I may choose not to treat. A 35or 45-year-old with SWAP defects and a little bit of elevated pressure, yes, I probably would treat. So, in the context of the patient and everything else built around it, I would treat based on repeatable SWAP loss.

Dr Burgoyne: A very practical question. One, do any of you use digital photos as opposed to 35-mm slides, and two, concerning your stereo-photos of the nerve, how do you view them in a stereo fashion?

Dr Caprioli: I still use film.

Dr Quigley: One of the things that is interesting is that we are probably entering an era where we will all switch over to some form of digital information, and yet I have photos of patients taken in our service in the 1950s, and you can still see the photos. You can still compare them with the old photos. I wonder how many of the technologies we are purchasing or seeing on the floor out here will still be there in 35 years. So the photos are going to have a longevity and an information content and value that is going to far exceed some of the software packages, even some of the companies that are selling these now.

Dr Cioffi: You can take the same type of photograph. You can have the same lenses up front. It is the capturing technology. I don’t think it has quite arrived yet. Layer on top of that the problems with storage. There was actually a fairly lengthy article on the plane out here yesterday in the New York Times about which storage media will survive and which won’t, and it is anyone’s guess. Finally, without going to extreme cost in digital, you are really hampered because silver grain still provides better resolution.

Dr Burgoyne: General question. Do you change treatment or make an intervention based on nerve fiber layer hemorrhage alone? Is a disc hemorrhage evidence enough of glaucomatous progression?

Dr Quigley: I change follow-up always. When someone has a disc hemorrhage, this means that we completely repeat everything about the patient that we hadn’t done recently. So, if we haven’t done a field recently, even if it wasn’t a visual field time, we will repeat it then. We will then see the patient every three months for a period of time. Because it is a sign that the patient is going to be progressive or is possibly progressive. We will also sit down with the patient, talk to him about cooperation with therapy. We might re-evaluate his pressure, his treatment. A lot of things happen. Do you always change the target at that point? No, I wouldn’t change the target to a lower number until I saw that something functional had changed. Saying that the disc hemorrhage is a sign of progression doesn’t mean that they all progress. There are a lot of patients who have a disc hemorrhage who don’t progress. So you don’t necessarily want to change the game, in my opinion, until you see that they have actually changed. But I start gathering a lot more information. They are waving red flags at you.

Dr Cioffi: I agree, structurally and functionally. I will take photographs shortly thereafter, maybe a couple of months later.

Dr Burgoyne: This has to do with the nerve fiber layer hemorrhage. Do any of you have an opinion about the increased incidence of disc hemorrhages in patients on anti-coagulants?

Dr Cioffi: I am not aware of any data on the increased incidence of disc hemorrhages with anti-coagulation, and I haven’t noticed it, off the cuff.

Dr Caprioli: I would agree. I think the incidence of disc hemorrhage is probably no different. Perhaps they are bigger if the patient is on anti-coagulation, but I think they probably occur at the same rate. But I don’t have any evidence to support this; it’s my clinical opinion.

Dr Burgoyne: Practically speaking, how do each of you measure, how do you assess the size of the disc in your clinical practices? What do you do, and how quantitative is it?

Dr Caprioli: We have quantitative techniques to measure this and we will be talking about this after the break, but to be very honest with you, I really don’t use these in most cases to make clinical decisions. With respect to evaluating how large

the optic nerve is in terms of interpreting what the width of the neural rim means, I sort of just look at it in a Gestalt kind of way and say this is a small nerve, this is an average nerve, this is a nerve that is a little big or a lot big, and I have maybe four or five categories, but I actually don’t measure them at the time of our clinical exam. As a back-up, we have these other quantitative techniques, but to be honest, I don’t use them to correct my examination of the nerve.

Dr Cioffi: I think the one thing I do, as was mentioned earlier, is that I make a note of asymmetry in nerve size. I don’t project a micrometer or any of that.

Dr Quigley: I have a micrometer scale which you can buy from Fischer Scientific that you can put inside the eye piece, certainly the Zeiss eye pieces in my slit lamp, and I wager you could probably do it in most other slit lamps as well. For about 12 years I have been measuring the size of every disc I see, in arbitrary units. Now, if you do that on the next hundred people you see, you will have established your own sort of normative database, and you will start to get an idea that the average size disc is, let’s say, 13, and one that is 11 is kind of small, and one that is 15 is rather large. Bear in mind that there is an optical magnification effect of high refractive error, so if someone is more than –4D or more than +4D, then there is going to be a magnification or minification that starts becoming important. But, in the general range of normal refraction, you don’t actually have to take account of anything, other than what it looks like on the measurement system. I have at least one referral a week for someone who is sent to me for asymmetric cupping. Or the patient has already been started on therapy when the asymmetry is explained by the size of the disc. Either both discs are large or one is larger than the other one, and that explains the asymmetry. In all these cases, we look at the nerve fiber layer and field, history, pressure, and everything else. And it is rare for me to tell them, “I’m sure you don’t have glaucoma”. But I can certainly reassure them that their findings are likely to be due to the fact that their disc diameter is large. Now the HRT actually gives you a disc area. It makes the same kinds of assumptions I just told you about in doing its calculation for disc area. We are noticing dramatic cases of patients with large physiological cups. They are particularly true in African Americans who are known from our population and other population studies to have larger diameter discs. The disc area is worth measuring, and you can do this with an optic nerve head analyzer, or you can do it with a cheap and dirty method similar to what I just described.

Dr Caprioli: We get lots of patients who are referred for: is this a glaucoma patient with large disc and large cups? A reminder, it is always useful to examine family members when you see discs like that. So, if you can find another first-degree relative who has the same size disc and the same looking cup and so forth, I think you need to worry less about the glaucoma.

Dr Burgoyne: One additional point I would make is that this brings us back to the discussion on the nerve fiber layer, because this is the kind of patient in whom the clinical nerve fiber layer exam really helps you feel confident when it looks healthy and abundant in the setting of a large central cup. I have to ask a question for myself. I always harp on to the residents that it is not the cup-to-disc ratio, much like Joe said earlier, rather it is the health of the remaining rim that leads me to

decide whether someone has damage or not. However, certainly the notion that the central cup enlarges in all directions without any change in the remaining rim has been described as part of glaucomatous damage. Do you guys know what I am talking about? Just the central cup getting bigger without the remaining rim tissue looking what I call thinned, bowed back, eventually excavated? How real is that in your experience?

Dr Cioffi: Are you talking about generalized cup enlargement?

Dr Burgoyne: Yes.

Dr Cioffi: I think it is real.

Dr Burgoyne: Where do you see it most commonly?

Dr Cioffi: I think there is some evidence in the literature that maybe up to 50% of early glaucomatous loss is diffuse. It is not only notching or dense nerve fiber layer bundle loss, but also you can have generalized cup enlargement. That said, I don’t actually even write cup-to-disc ratios on my chart. I think they are generally worthless, and so I make detailed drawings and take photographs. I think diffuse nerve loss and generalized cup enlargement occurs.

Dr Caprioli: I’d go one step further. I think there is probably some component of diffuse loss in every patient with progressive damage from glaucoma. Sometimes this may be vastly overshadowed by relative focal loss at one of the poles, but almost invariably, if you look carefully as the patient progresses, there is some temporal thinning and some nasal thinning which is often overlooked because of the rather glaring defects at the poles.

Dr Quigley: Claude, we did a study of progressive change in the disc and we had annual photographs. We looked at 100 people who got worse. In something like 50% of them, there was a highly localized loss which disappeared and merged into a more diffuse pattern within the two years after it first appeared. So, they often had a notch or a wedge-shaped defect of the nerve fiber layer, sometimes with a hemorrhage, and they would go from a 0.5 cup to the localized defect over a period of time, but if you didn’t see the patient during that period of time and two years later you looked, you would see a diffuse 0.7 looking cup. The second comment I would make is that we now know that there is something called secondary degeneration in the visual system, as there is in the brain, which means that when some ganglion cells die, they take out some buddies as they go, from the production of some sort of toxic environment. The extent to which this is going to occur in a broader area around the retina, maybe even diffusely across to the other side of the retina, means, as Joe says, that there is always going to be diffuse loss, not just highly focal local loss. Our histological studies never showed an eye that had loss in only one place, within the limits that you can measure that stuff in laboratory studies.

Dr Cioffi: I want to make a point. In collecting these eyebank eyes, we get a fair number of them, I am stunned to see, because we get the full medical record of

these patients, I am stunned to see how infrequently optic nerve photographs are taken. I would urge you, if you are not taking them, to start using them. I think you will really find them to be a nice addition to the care of your glaucoma patient. In fact, in the last two weeks, I just received the first chart with a set of photographs. I don’t know, maybe it is our particular area, but these are patients being taken care of in a metropolitan environment and they are not getting photographs. So I really urge you to start using them.

Dr Burgoyne: I think that brings this part of the program to a close. I wish it could keep going. Thank you very much to all the participants.

Workshop

Imaging the optic nerve head and nerve fiber layer in glaucoma

J. Caprioli, MD and Harry Quigley, MD

Dr Quigley: We were just privileged to be at the Glaucoma Society Meeting and Jeff Liebmann did a study in which he looked at a group of patients before and after LASIK and imaged them with three different machines: the GDx Nerve Fiber Analyzer (GDx, scanning laser polarimetry), Heidelberg Retina Tomography (HRT, confocal scanning laser tomography), and Optical Coherence Tomograph (OCT). There was no statistical difference before or after LASIK when imaging was performed with either the OCT or HRT. However, there was a difference when imagining was performed with the GDx. We think this is because the corneal polarization shift would be changed if you thin the cornea by a certain amount, or the healing response in the cornea somehow changed the cornea’s response, but the nerve fiber layer was the same. So, an instrument that has a corneal component might very well be changed, but probably the other images aren’t bothered by it.

Dr Caprioli: Let us explain a little bit more about what we mean by this corneal artifact. The GDx deals with corneal birefringence by using a compensator, which is fixed. In other words, it assumes a population average for the magnitude and the direction of the polarization in the cornea, and applies this to every single patient. As a first approximation, it probably wasn’t too bad an assumption, but it turns out that the corneal birefringence really represents somewhat of a bellshaped curve, both with respect to the magnitude and the direction of the polarization, and that a single standard correction just doesn’t work for everyone. One size does not fit all. We have come to the conclusion, and I know GDx has also, that there needs to be individual compensation for each patient, based on his or her corneal birefringence in each eye. I think Harry and I are both hopeful that this will correct a large part of the problem and get back to the original results, where Harry Quigley and Bob Weinreb found good correlation between the anatomy and the change in polarization properties.

Dr Quigley: I don’t mean to beat on only one instrument. We can talk about good and bad. OCT has shown some really beautiful images of a variety of retinal conditions. For it to be useful to us in glaucoma, though, as Joe Caprioli said, it has to be a little more user-friendly. The OCT instrument judges the nerve fiber layer

Glaucoma in the New Millennium, pp. 129–132

Proceedings of the 50th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, April 6-8, 2001

edited by Jonathan Nussdorf

© 2003 Kugler Publications, The Hague, The Netherlands

thickness almost by a kind of arbitrary choice as to, “Well, this is a different color here and it has different optical properties, so that is probably where the nerve fiber layer is”. But there is no particular reason to think that this was a good judgment, except that it worked. Joel Schuman went to the extent of producing nerve fiber loss in a monkey model of glaucoma and then OCT’d those eyes and measured them histologically, and the choices they made with the OCT for what is arbitrarily the nerve fiber layer really looked pretty good. In ideal circumstances, the OCT has also been validated as something that shows how much nerve fiber layer there is. It remains to be seen whether the commercial models that you are getting of that machine are going to do it that well, and whether they are going to continue to update and upgrade software in the kinds of ways that maybe we were suggesting, or in brighter ways than we can think of today for using the machine more effectively.

Dr Caprioli: As long as we are pointing out negatives, let me do one for the HRT so that we are fair about it. As I mentioned, the HRT measures the surface, the position of the surface. In terms of its axial resolution, it is the poorest of these instruments. It cannot measure thickness, and its ability to discriminate two points separated in the Z axis, away from you as you are looking into the eye, is actually pretty poor. It is only about 300 µm, and in an eye with good optical characteristics. These instruments are all trying to come up with ways of measuring early damage, but by very different approaches. Each has its good points and its bad points. Remember those ROC curves I showed you comparing the results from the different instruments with respect to the relative sensitivities and specificities? We actually get something very close to that top left-hand corner with a 99% area under the curve. It is right up at the top left-hand corner, if we add the results of all three instruments. Now that’s not a very practical approach because it is so time-consuming, but it does indicate that each of these instruments is measuring something a little different.

Question: When you look at your GDx printout, what parameters do you rely on?

Dr Quigley: In analyzing study data, when we know that one group is glaucomatous and the other is normal, the actual absolute values of the nerve fiber layer thickness from the machine are not terribly useful to me. If you look at which thing is the best single identifier, or which group of information, first the absolute nerve fiber layer thickness is what the machine is trying to measure. However, this is probably not your best indicator. It would be like saying, “In the Humphrey machine, how good is the gray scale?” The gray scale is the absolute decibel. That is the sensitivity of the patient measured in decibels. But what we have learned with the Humphrey is that you have to compare it to a normative database, and do statistics to find out how likely it is that that value for that patient is abnormal. For me, the number that is most useful is the neural network number in each patient. In general, the value I was showing you here is that the cut point in two large studies we have done, and I think that this is similar in other people’s data, is somewhere in the twenties. So that someone with their number in the 10, 12, 15 range is much more likely to be normal than not. Someone whose number is 40 or 50 is much more likely to have glaucoma.

Question: If the number is abnormal in the glaucoma suspect, with borderline intraocular pressure, normal visual fields, would you start him on treatment?

Dr Quigley: No. I would not simply rely on one instrument’s number.

Dr Caprioli: I think one of the questions I have seen written down somewhere, perhaps to us as speakers, was do we really use any of these instruments to make diagnostic or clinical decisions? I assume that means alone, or does it modify what we would have done otherwise if we didn’t have the results from that instrument? I have, and, of course, Dr Quigley has, research interests in these, and we make these measurements all the time in patients. To be honest, I fall back on standard clinical examinations of the optic nerve and the disc photos for making the vast majority of clinical decisions. I certainly would not make a clinical decision based on a measurement from any of these instruments alone.

Dr Quigley: I couldn’t agree with you more, and I think that, when someone buys an instrument, you tend to say, “Well gee, I invested my energy in this and the patient went through the examination, so I really ought to act on it”. Use everything you know about the patient when making your decision. If you were on the fence and you thought there was a suspicious disc and there is an iffy field defect and it is an ocular hypertensive and one of these machines is also screaming abnormal, that may be the thing that pushes you over into finally putting the picture together as a definite person you suggest therapy to. But, if you are looking at a normal disc and nerve fiber layer and a normal visual field, and one of these instruments is screaming ‘abnormal’, don’t necessarily buy the farm on that one.

Question: One of the things that is uppermost in most practitioners’ offices is that the reps are bombarding all the practices to buy the GDx or one of these machines. The insurance companies are reimbursing these machines. I know quite a few practices that are considering stopping taking the disc photography because it is so time-consuming to dilate the pupil, etc., and using the HRT or the GDx instead. Is this something that you would advise practices to do, or is the technology not there right now for general practice?

Dr Caprioli: The first part of that question I might just address by saying that, if you don’t have one of these things, you are really not missing out on very much. As long as you are looking at the disc and the nerve fiber layer, and so forth, you are going to be taking good care of that glaucoma patient, and you are not missing out on something that one of these instruments is going to tell you. The second part of the question, based on what I just said, I wouldn’t run out and get one of these things. You are under a lot of pressure from the commercial interests to go ahead and do it. If you have an interest in the technique, I think it is a lot of fun to use, it is very interesting, it is an interesting approach. You may even want to do some research with it within your own practice, to see how it compares with other techniques. I think that’s great, but you have to use it like any other laboratory result or test. You have to take it with the caveats that come along with it.

Dr Quigley: I am going to add a couple of things. If a doctor is taking care of his or her patients based on pressure from a commercial sales person, I think that is

deplorable. It happens to all of us, and it works, but it shouldn’t work. So, think that over. Think over your relationship with the detail person and the sales person, and think about what you know and what they know. You know best what you want to do for your patients. The truth is, from the point of view of these instruments right now, because there is reimbursement from some of the carriers and from Medicare for this, you are in the enviable position that you won’t lose money imaging people. So when I say ‘enviable position’, this means that you can either recommend it for your patient or not, without your patient necessarily having to pay a lot of money for it, although they are going to get nailed for deductibles in some insurance situations, and you are not going to make a lot of money out of imaging patients. One of the reasons you’re not going to is, if you begin thinking in your mind, “Gee, I am going to buy one of these and make a million by imaging everyone who walks in”, be sure you cost out how much the color printer costs to print these images. Because we are spending several hundred dollars a month on color printer cartridges. There are a lot of hidden costs that you’d better look at before you think you’ll make a lot of money. But I think you should have some way of documenting the patient’s disc. As Joe said, you can take care of people in a lot of good ways. The HRT, for example, produces a very usable image of the disc quickly and effectively. The GDx produces a pseudo-color image of the optic disc. It is not stereo. It probably doesn’t have the quality or ability to detect excavation change and a notch, and that sort of thing, but it is better than nothing. If you are presently not doing fundus photography, and you don’t intend to, then owning one of these instruments is better.

Dr Caprioli: The second part I wanted to address was whether you can change from doing disc photos to getting one of these instruments instead. I have been using these sorts of approaches for a long time now. It has been a major interest of mine. I would not feel comfortable, having been doing disc photographs and continuing to do disc photographs, just switching to HRT or GDx, or any of these things, alone without the disc photograph. Certainly, as Harry said, if you are not doing it and now you’re doing HRT, I think that’s a big step up. But I wouldn’t feel comfortable switching from disc photographs to one of these techniques, and omitting the disc photograph.

Dr Quigley: As a matter of practice management, the New York Times news service carried an article on the GDx within the last month. How many patients carried that article into your office? They bring it to me all the time. They say, “Why aren’t you doing this test, Doctor?” It can make you feel like, “Maybe I’m behind the times.” “Maybe I should have something like this.” As Joe said, you don’t necessarily have to do it, but you wouldn’t be losing money if you did. And there is value in it. My guess is that, among these instruments, one or more is going to be a good long-term addition to glaucoma management. We just can’t tell you yet. You have heard an awful lot today, so you have a pretty good idea of what we think about them. I think we are being fair about it, plus or minus.

Round table

My most confusing optic nerve head

Jonathan Nussdorf, MD, presiding

Panel: George A. (Jack) Cioffi, MD

Paul Palmberg, MD, PhD

Harry A. Quigley, MD

Dr Cioffi: This round table focuses on my most difficult optic nerve. I didn’t think I could do this round table without a few pictures, so I thought, for Harry and Paul, I would present a few patients and let them comment, because these are the type of folks you will be seeing in your office.

This patient is a 31-year-old Japanese American who came in about eight years ago (Figs. 1a and b). He is a –8.00 D in both eyes, and is 20/20 in each eye. He has had exams by a variety of different people. He saw Steve Drance at one point. He is a VP with a computer company. He has never had a pressure above 20. His

Fig. 1. Right optic disc image of a 31-year-old Japanese American with myopia (-8.00 D OU, 20/ 20 OU) and kissing inferior and superior visual field defects in this eye. a. The appearance of an ‘oblique exit disc’ with nerve fiber layer loss. b. Comparison between the right and left discs demonstrates relative disc size asymmetry within a given patient.

pressures in my office on a diurnal ran between 16 and 20. His angles are open. His visual field in this eye (OD) has about a 22-decibel mean deviation loss, and in the other eye (OS) about a 10 or 12. My question for the panelists is, how do you go about following and treating and prognosticating about such patients? Paul?

Glaucoma in the New Millennium, pp. 133–147

Proceedings of the 50th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, April 6-8, 2001

edited by Jonathan Nussdorf

© 2003 Kugler Publications, The Hague, The Netherlands

Dr Palmberg: I think it clearly is glaucoma, and it is someone whose nerves are abnormally susceptible. The right optic nerve head looks a little large too (Fig. 1a). I don’t know if that plays any role in it. We saw laminar dots going all the way out almost to the superior pole. We get some peripapillary atrophy in which you can see choroidal vessels through missing retinal pigment epithelium and I think Doug Anderson has shown that, in people who are called normal-tension glaucoma, you see that four times more often than you do in people in the general population of the same age. He has speculated that such eyes may be at greater risk for loss of autoregulation since they are being exposed to vasoactive substances through the choroid there. But after you put all that together, you are just saying, this is somebody for whom 20 is too high and we’d like to lower it a lot, because they have a lot of damage.

Dr Cioffi: Now this was in 1992, Paul. What were you doing in 1992?

Dr Palmberg: For these people with a pressure of 20, in 1992 I was giving whatever drugs we had and if that didn’t work... This is a 31-year-old, so I probably would not have done laser. Let’s just say that, with the drugs available in 1992, which would have been beta-blockers, miotics, Diamox, we would probably eventually have ended up doing a filtering procedure with either 5-FU or mitomycin to try to get that pressure down 30%.

Dr Quigley: Let’s go back to the actual disc appearance, because if you contrast...

why did Paul think this disc was big? Compare the two discs. Flick back and forth if you would, Jack, between the two (Figs. 1a and b). The actual disc margin of the right eye is from there to approximately there, if you were marking it with the HRT. This is the beginning of the choroid. You are looking at choroid over here. That’s the end of the retinal pigmented epithelium. This is a little bit of downsloping temporal rim, so the disc horizontally goes from here to there, and what I am marking is the actual outlet for axons out of the eye. Let’s think mentally. How big is this from here to here and we will go back to the preceding picture. In this eye, that is the 12 o’clock position and that’s the 6 o’clock. The right disc is probably 50 or 60% larger in diameter than the left disc. So, discs can vary, not only from one human to the next, but also often between both eyes of the same person. Second, you see this sloping crescent over on this side, quite typically seen in high myopes, though moderate myopes don’t necessarily have it. What is going on is that the disc has an optic nerve leaving the back of the eye, not straight out the back of the eye, at a 90° angle, but at a severe tilt, so we call them oblique exit discs. That gives you a royal pain trying to figure out what the cup to disc ratio is, because you won’t see a sharp margin on the cup. The first question you might ask yourself is, “Am I sure I am looking at glaucoma?”, because it could simply be an oblique exit disc in a high myope and you pass it. Now the asymmetry would be very striking to you, but the asymmetry is due to the difference in disc size. It isn’t that this disc is really damaged because the cup is so much bigger, because it started out life with a bigger cup than the other eye. However, in this color picture, there is a striking absence of the nerve fiber layer (Fig. 1a). In fact, there is a focal loss in here that is quite dramatic. See the nerve fibers there, but you don’t see them here (look between 7 and 8 o’clock). You ought to see them in both places. There are no nerve fibers at all down here. This guy is going to have

field loss. He has field loss in his upper field corresponding to this zone, and probably has field loss in the lower zone as well. He probably has kissing defects above and below around his 20/20 vision.

Dr Cioffi: Actually, that’s right on. I don’t have the fields. They are on my computer, but that is exactly right on.

Dr Quigley: The other eye probably has an iffy early field defect. So what tells us that this is a glaucomatous disc? It is the absence of the nerve fiber layer and the field defect. You would have gotten a field on this patient and say, okay, it’s more than an oblique exit disc because simple oblique exit discs don’t get double arcuate scotomas.

Dr Palmberg: The other thing that correlates exactly with what Harry is saying, is that these laminar dots are pale. This temporal sloping crescent is never going to look as pink as it would if the nerve was coming straight up at you, but you have laminar dots here that come almost all the way to the inferior rim and some up here as well. As George Spaeth pointed out a long time ago, that’s also a sign of missing tissue, that there used to be nerve tissue coming through and obscuring these dots, and now you can see them clearly. There is no tissue there to obscure the lamina structure. So what’s missing here in the nerve fiber layer is also missing in the laminar dots.

Dr Quigley: The next thing that occurs to me in evaluating this fellow is the fact that he is Japanese. We know that, on a population basis, persons from Japan have an average eye pressure of 13. So, a fellow with a diurnal that is averaging between 16 and 20 is approximately four to five points above the average person, as measured in his ethnicity. This is equivalent to a European person having pressure in the low twenties. This person is actually a higher pressure glaucoma subject compared to the average person with glaucoma in Japan, whose ‘high’ eye pressure is more like 15.

Dr Cioffi: What would you have done here?

Dr Quigley: I agree with everything Paul said. You want to lower the eye pressure. The target for a guy who is running 16 to 20, his baseline is 18, so 50% lowering would be 12. I would try to put him in the 12-13-14 range. If you could get him there, now you probably could get him there medically, but you would probably wind up heading in the direction of a surgery. You are terrorized doing that, by the way, because he has a bunch of risk factors for being the person who is going to get hypotony, maculopathy, or nasty consequences from getting a filtering operation with a big bleb. Is he a contact lens wearer?

Dr Cioffi: Of course.

Dr Quigley: Yes, okay, so now you are even more in the soup, because you have someone who doesn’t want to have a bleb or whom you are forced to tell, “You keep wearing contact lenses and you are at somewhat greater risk of a leak and bleb-associated endophthalmitis”. He is also going to ask you the question, “Doc-

tor, how long is this filtering operation going to last? I am 31 years old. Is it going to last for 50 years. I am planning to live to be 85. My mom is 90.” The answer I give to that question, by the way, and I don’t know if it’s a smart answer, but it is that, every five years since I have been in practice in glaucoma, we have had a fair improvement in some major aspect of how we take care of glaucoma, whether this was laser treatment or trabeculectomy or mitomycin added to what we do. I don’t know what is going to be true in 50 years’ time and neither does he, but I know that if he doesn’t get his pressure lowered pretty soon, it’s not going to matter. He ought to take his best shot with our best therapy at this time, and not worry about what is going to happen in 50 years if we don’t take care of it now. I don’t know if that would help you in dealing with this. If your patients don’t ask that question, you’re lucky. Mine ask it all the time.

Dr Cioffi: That’s great. That is exactly what we did. We did a filter on his right eye in, I think, 1992. He has had a pressure running around 10 ever since and has had absolutely stable visual fields, no change. About two to three years ago, I ended up doing his left eye because of change. He wouldn’t tolerate beta-blockers at the time. Of course, we didn’t have the other drugs.

Dr Quigley: How did you deal with his contact lenses in the filter?

Dr Cioffi: You know, there’s no way around that and actually we had some discussion the other day about whether this is a LASIK patient, or a photorefractive patient at all. He now wears lenses intermittently with blebs in both eyes, and understands the risk, and I try to get him to wear his glasses as much as possible, but his vision is just so much better with his contact lenses. This is a high-powered guy. He is a mover and a shaker. Let me tell you one thing he did in about 1994; he learned Braille. There is a realist. He came in one day with his wife who is about the same age. They had two or three young children. He announces to me with the whole family standing there, “Oh by the way, I just started learning Braille”. There’s a stroke for your confidence.

Dr Palmberg: I’m such an upbeat guy, I probably would have told him, “Well, look, our filters are probably going to accelerate cataracts, and when they do, we could put an intraocular lens in and you won’t have to wear your contacts any more”.

Dr Cioffi: We haven’t operated on his lenses yet.

Dr Quigley: By the way, be sure that you remember to tell this guy that all his family members, including his children, ought to get examined. One of my favorite patients is a gentleman just like this, with pressures actually in the 40 range, who was in his late thirties. He had bilateral filters and fortunately they were going well and, therefore, he kept coming back, and I said, “Do you have any brothers or sisters?” “No.” “How old are your kids?” “Well, they are 11 and 8, two boys.” He said, “Well, should they get examined?” I said, “Why don’t you bring them in?” So the 11-year-old had a pressure of 32 and the 8-year-old a pressure of 26. Subsequently, before they were 20 years old, both of those boys wound up being filtered, and I probably would find a Glc 1a gene defect in that family if we were to look for it. We didn’t know about that then.

Dr Cioffi: That’s a very nice point. Let me add to the discussion. This guy obviously became quite concerned with young children. He wanted to do something. He became sort of one of our poster children for a capital campaign for raising money, and his parents came into town for the talks, and he said, “You know, why don’t we just screen my dad. He can be part of your normative population for some visual field test.” Guess what. He had actually much worse field defects in both eyes and was unrecognized.

Dr Quigley: The Academy is presently working on a program through which we are going to be surveying ophthalmologists to see how aggressively they chase down the family history of their glaucoma patients. If we made it easier for patients to get their family members examined, we would have a very good yield of persons like this guy’s father and the children of my patient, who were detected earlier and got better therapy. We are investigating that process right now, and I can tell you that it looks as if there is a less than ideal ascertainment of family members who might have glaucoma.

Dr Cioffi: Let me move on to the next patient so that we get a few nerves here. This is a 30-year-old Caucasian female. She is a +3.00 D in both eyes, 20/20 OU. She has pressures of 22 mmHg in both eyes and she has this disc on the right (Fig. 2a) and the left (Fig. 2b). She has just a little bit of far peripheral loss on her fields that were repeatable, but not really arcuate in nature, inferior in both eyes.

Fig. 2. Images from a 30-year-old Caucasian female with hyperopia (+3.00 D) and bilateral visual field defects illustrate asymmetric cupping in the presence of optic nerve drusen which are: a. more apparent in the right eye; and b. slightly buried and hidden from view in the left eye. Optic nerve drusen are relatively more common in small optic nerve heads.

Dr Palmberg: It looks to me as though there is an odd coloration to this disc. You have what looks like white balls up there at about 11 o’clock and at about three or four o’clock (Fig. 2a), so I am beginning to wonder if the pressure of 22 is sort of a red herring and maybe we’re looking at optic nerve drusen. I would like to get an ultrasound and see if there is some calcium there.

Dr Cioffi: So I got an ultrasound, and yes, in fact, she does have optic nerve drusen.

Dr Quigley: Get used to the fact that, when you look at a disc in a patient, you say

to yourself, is it a big disc or a small disc, or an average size one? Look at that photograph. Assume that it is not an optical illusion that is going on here, but you really could judge whether that is a large or a small disc. Very small discs are more likely to have disc drusen. So the 0.4 or 0.5 cup in the left eye (we are trying to guess depth here from the position of the vessels in a single image) – but perhaps even bigger because it looks as if there may be undermined rim right there – so, maybe this cup is even as big as 0.6 or 0.7. That’s huge in a person who has a small disc, way out of proportion to what would ever be physiological. So we have to be concerned. The arterioles are also narrow here. If you read nerve fiber layer, there is very little nerve fiber layer there. This is somebody who probably has two optic neuropathies, without question disc drusen, as Paul noticed. I don’t see drusen in this eye (Fig. 2b).

Dr Cioffi: She actually has some on ultrasound in this eye as well.

Dr Quigley: They are kind of buried, but I am really worried that you have somebody now who has two other risk factors for glaucoma. The eye pressure being 22 is a risk factor. It doesn’t mean she has the disease. I am looking at asymmetric cup size with the cup size in the left eye being way out of proportion to what ought to be there in a small disc.

Dr Palmberg: Could it be the other way? The other cup to disc ratio would have been 0.3 or 0.4 if you hadn’t had the drusen.

Dr Quigley: Yes, the drusen fills everything in.

Dr Cioffi: Both eyes had sort of nondescript peripheral visual field changes. The right eye was a little worse than the left in terms of the field, but nothing that make you say, “Ah ah, that’s glaucoma!”

Dr Quigley: And you did gonioscope the patient?

Dr Cioffi: She is open in both eyes. What do you do with drusen patients with nondescript visual fields and a pressure of 22? Do you treat them all?

Dr Quigley: Yes, I do.

Dr Palmberg: I do because I’m not going to know if they get worse due to pressure. The whole idea of not treating ocular hypertensives is based on the idea that this patient is normal now and I will be able to detect it before they change in any important amount. So if a patient has a cataract and ocular hypertension or other disc findings and you can’t figure out what is going on, then I would treat it mildly.

Dr Cioffi: We do exactly that same thing. The patient is on beta-blockers, her pressures have come down into the mid to low teens. I agree with both of you, and that is exactly what we do in practice, we treat these patients. An ocular hypertensive with drusen I always treat.

This gentleman is 35 years old. He has a past medical history that is significant

Fig. 3. Image of the right ‘tomato ketchup’ fundus of a 35-year-old male with unilateral glaucoma OD and a history of seizures associated with Sturge-Weber syndrome.

for seizures. He is –2.00 D myope in both eyes, and 20/20 OU. In his right eye, he has had pressures ranging anywhere from 24 to 34 (Fig. 3). In his left eye, he is always 16 to 18. He really can’t do automated visual fields, and confrontational fields are grossly normal. That is all I have to go on.

Dr Palmberg: Afferent defect?

Dr Cioffi: He doesn’t have an afferent defect. I don’t actually have a picture of his left eye.

Dr Palmberg: If you showed him a flashlight, would he say that it looked only 80% as bright in this eye as the other?

Dr Cioffi: No, he doesn’t give subjective or objective afferent findings.

Dr Quigley: Does the fundus on this side look more tomato-colored than on the other side?

Dr Cioffi: Oh, this guy is good. I don’t know, what do you think?

Dr Quigley: Well, this is kind of red. There is a little bit of torturous vascularity. You have a fellow who has central nervous system disease with seizures. He has a monocular glaucoma. You’d be thinking, do his episcleral vessels look kind of funny? Perhaps he has a red splotch on the side of his face, something like that.

Dr Cioffi: So-called tomato ketchup fundus. I can’t put anything past this guy.

Dr Quigley: This is an interesting issue, because they can have glaucoma on both sides, and I have a couple where the red splotch is only on one side and the

glaucoma is on both. And very interesting questions about how to manage this particular issue.

Dr Cioffi: What do you do with these, Paul?

Dr Palmberg: Well, you try to lower the pressure with about the same kind of criteria. If you do get to filtering surgery, you would be darn sure to do a posterior sclerotomy or use a Baerveldt implant so that you have a very minimal time of lowered pressures. Harry mentioned the other day that if you are going to use a scleral flap, have stitches in place to pull up immediately. You don’t want a low pressure in this eye for more than a few seconds.

Dr Cioffi: It seems to be the exception that I can treat these guys with medicine, and I think a lot of them end up with surgical intervention, as this fellow did, and he had a trabeculectomy. I find that often when you operate on episcleral venous pressure patients, their blebs don’t look too great, but they often work very well.

Dr Palmberg: When you see vessels on the conjunctiva, like a rete mirabile, that layer is under the conjunctiva separated from it, and when you cauterize it, it doesn’t bleed. It is amazing. You would think that you were going to have a lot of trouble with surface bleeding affecting your bleb, but it doesn’t seem to happen.

Dr Cioffi: This is an 84-year-old Caucasian male. He is pseudophakic bilaterally. He is NLP in his right eye from glaucoma. He is 20/40 in this left eye. His pressures are 14 to 16. He is on three topical medications. He has had ALT for 360° in this eye, and he has a 5° central field. How do you follow these guys? He is 14 to 16, so he is starting to get down into Paul’s window. I know everybody in Miami has pressures of 12.

Dr Quigley: What was his baseline IOP?

Dr Cioffi: It was in the mid to high twenties.

Dr Quigley: One of the difficulties is that, if you acquire a patient who has been under therapy from someone else, you don’t actually know what their baseline eye pressure is. If the fellow’s pressure is 16, it could be that this is what it always was. My first move is usually to try to talk the patient into stopping their medicine in one eye. That is not often easy. Not only do they not comply with therapy, but also they will refuse to stop it, even though they are not taking it half the time.

Dr Cioffi: Harry, if this was your eye and you were 84 and on three medicines and blind in the other eye, would you stop your three medicines?

Dr Quigley: No, our approach to this patient would be to start doing a 10-2 Humphrey field with foveal sensitivity measurements about every two months for a year, and if the person had absolutely no change during that time, I’d say, “Damn, I’m smart that I didn’t operate on this man”. I would continue 10-2 testing, and extend the time interval to maybe every four months for the next year

after that. If there were signs after three or four of those that he was losing it further, then you have to bite the bullet and do the filter.

Dr Palmberg: You might be able to stop the medication in the other eye that is already NLP, just to see how high that would go. You would like to know whether the fields have been progressing. Get the records and find out.

Dr Cioffi: It’s tough with a 5° field on a Humphrey 24-2 or a 30-2, and I actually do exactly what Harry does. I move on to a Humphrey 10-2 with the fovea sensitivity on, and that is how I follow these sort of end-stage visual fields where the optic nerve itself isn’t going to tell you much.

Dr Cioffi: I think that’s it for the optic nerves. Regrettably, I have to go catch a plane. Thank you again all for your hospitality and I am sure that Harry and Paul can handle all the questions. Thanks.

Dr Palmberg: While we are waiting for the question session to start, I’d like to chime in as the others did and thank you for the honor of being invited here and for the incredible hospitality of the hosts, and to say how much I have enjoyed being part of this.

Question and Answer Session

Dr Nussdorf: What causes a disc hemorrhage? Is it due to ischemia or is it a precursor to ischemia, and is the blood toxic to the never fibers?

Dr Palmberg: Well, neither one of us knows, but if the problem in glaucoma is a problem with autoregulation or blood flow, then it might be that, as in people with migraine headaches, they have a constriction followed by a dilation. It could be that, after an episode of vasospasm followed by vasodilation, you might have a rush of blood and your surge protectors aren’t working very well and you would get a little hemorrhage in that location. I saw a patient not too long ago, and I am sure all of us have, who at the time following filtering surgery when the pressure is lower, developed an absolutely classic disc hemorrhage at the time that the eye’s pressure was lowered from about 26 down to 12 or 13. Again, the idea of perhaps a constriction followed by a surge, you might get a hemorrhage. I think there is another odd thing about people with normal-tension glaucoma, corrected for age and everything, they are more likely to have suprachoroidal hemorrhages than people who have primary open-angle glaucoma, but their pressures were around 18 and they were progressing. So I kind of wonder about vascular spasm followed by dilation. All of this is total speculation.

Dr Quigley: The question about disc hemorrhage could be added to a little bit by saying that if you take a monkey’s eye and raise the eye pressure to 40, you will sometimes see a disc hemorrhage appear during the time the monkey is losing nerve fibers. I have no reason to think that a healthy young monkey has an autoregulatory problem. So, at least in that artificial laboratory model setting, it is something to do with losing nerve fibers and the process of glaucoma that causes

the hemorrhage. Now I have speculated in some diagrams in print that there is a continuous meshwork of capillaries that goes from the retina down into the disc and into the optic nerve, and as that whole structure recedes out of the eye in the process of excavation, the capillaries are put on a stretch because they pull backwards by about half a millimeter, the whole capillary network is on a strain from being physically pulled on. In addition to this stretch, the thing that is in between all the capillaries is nerve fibers and they are being lost. So there is less support for them to be sitting there. It makes some sense then that you could just have a tearing of a capillary leading to a flame-shaped hemorrhage.

It is absolutely not good to have an open blood vessel leaking serum into the nerve fiber layer. When God built the retina and the central nervous system, she made sure there was an intact blood-brain barrier and that there was no serum protein getting in loose among the neurons. It is probably bad for the neurons to have that happen, absolutely. Of course, the whole process is bad. We know that from a practical standpoint, from a clinical management point of view, that is a patient you have to watch more closely. It could be ischemic too, I don’t know.

Dr Nussdorf: If the blood is bad, why don’t patients with bad diabetic retinopathy get horrible optic neuropathies?

Dr Quigley: Diabetic retinopathy patients do get horrible neuropathies. Some years ago we began counting the optic nerve axonal number in human eyes. And we would get eyes from the eye bank. One of the things we learned very quickly was that if we used eyes from persons who had a history of diabetes, even without visible retinopathy in the retina that we got in the fixed state, and we looked at the eyes with diabetes, they invariably had lower optic nerve counts than control nondiabetic eyes. It is my opinion, without having published this and documenting it in a tight way, that diabetics lose ganglion cells and inner retina at a much higher rate than other people do. But they get retinal neuropathies that are sometimes worse than you would expect from their lack of diabetic retinopathy, as we see it.

Dr Nussdorf: What else do you tell your patients to do, other than to control their intraocular pressures? Do you tell them not to eat Chinese food?

Dr Quigley: Actually, the ingestion of monosodium glutamate is a terrifically bad thing for you to do, in part because of the salt load. There is a tremendous amount of sodium in MSG, so I would tell patients, go and enjoy Chinese cooked food, but tell them no MSG, and the chef will have heard that a thousand times and will abide by it. Ingesting oral glutamate is almost certainly not going to cause any damage to your eye from the glutamate itself, because your eye has a beautiful set of systems for getting rid of glutamate. It is one of the reasons why it is unlikely we’re actually going to confirm that there are high glutamate levels in the vitreous in experimental glaucoma. We have just finished studies of more than 100 rats with experimental glaucoma, and while there is some elevation of glutamate in the vitreous cavity of eyes of rats with glaucoma, there is elevation of a bunch of other amino acids as well. It is not a specific spike of glutamate, and it doesn’t seem to correlate with a lot of things regarding the damage in the eyes of those rats. I think it is a relatively non-specific elevation of a bunch of amino acids. That doesn’t mean that glutamate excitotoxicity isn’t related to glaucoma. It simply means it is

unlikely that you are going to be able to have the simple result that, “Hey, there’s a lot of glutamate floating around in the eye”. It is going to be more complex than that.

To answer the question specifically, I tell all my patients to exercise. There is a clear relationship between someone’s aerobic activity and their eye pressure. There are two studies, one in normals and one in older persons who were ocular hypertensive, that show that you can lower your eye pressure with some regularity by another point or two with aerobic exercise, not necessarily jogging or running five miles. But this was a group of mature persons who had a walking program where they raised their pulse to an aerobic level for 20 minutes four times a week. People respond to that very well. They want something to do other than simply lowering the eye pressure. Beyond that, altering any other aspect of your life, use of the eyes is irrelevant, caffeine or alcohol in moderation is irrelevant. God knows how people live in New Orleans. Most of the other things that people do, I can’t tell them one way or the other. There is this whole pharmacopeia of Echinacea, St John’s Wort, Ginkgo Biloba, which I tell them to stay away from because they are expensive and a waste of time.

Dr Palmberg: The only other thing I tell people who have rather advanced damage is to think about not drinking more than one or two glasses of fluid in an hour. Occasionally somebody will come in and their pressure is like 28, and it has always been 20. And you say, what were you doing in the last hour? And they say well, just sitting out there waiting, and I drank an entire liter bottle of Coca-Cola or something. I don’t know that having the pressure up for half an hour or an hour until the kidney catches up is a bad thing. I tell them the total amount of fluid you take in during the day is not harmful, but it is probably better not to drink more than one or two glasses in an hour in people who have rather advanced glaucoma, because you can raise the eye pressure that way.

Dr Quigley: There are some other things we have in a brochure that we hand out to patients. It deals with those whose exercise will very often be weight-lifting, and you do not want them to lift weights with a closed glottis. You don’t want them doing (strains here) kinds of activities. They can breathe through weight-lifting just fine. Some of them are on the decline bench. Their head is below their heart. There should be no activity for a glaucoma patient in which their head is below their heart. Everything that is fun that you want to do can be done in the horizontal position, or with your head above your heart. And so, go right ahead and do all the exercise in the world.

Dr Palmberg: I tell them that, as far as we know, Viagra is not a problem.

Dr Quigley: Steroids are a huge issue. Please do ask your patients what drugs they are taking, and you want to know everything. You want to know the nasal sprays and the inhalers. These have now been proven through epidemiological evidence to be associated with the onset of glaucoma in persons in a large study in Canada. So you should minimize the use of those. It is fine for someone to use them, as long as you are monitoring them and you know whether they are having a pressureelevating effect. You shouldn’t say, “Don’t ever use anything with steroids”,

rather you should say, “If you start using steroids, I want to recheck your eye pressure to see if it has changed”.

Dr Palmberg: I also try a couple of things. Tell patients who are using medications a couple of times a day not to look at the clock, but to take this medication with meals – breakfast and dinner – because I think people remember to eat meals, and I don’t think they think about looking at clocks. Of course, I also instruct them to space their drops out over time. I also show them how to put drops in. I find it is really surprising how many people who have had glaucoma for 10 or 15 years have no clue how to get a drop in their eye. And you watch them and they are actually missing. So I tell them to take one hand, put it on their cheek just below the eye, pull down the lid to make a little sack, bunch up their knuckles, take the bottle upside down with the cap off in the other hand and put their knuckles right on top and tilt the head back and lay the palm of the hand that is holding the bottle on top of the knuckles from the other and lean back, and by golly you can’t miss. Because the hand knows where it is. The other hand is in contact with this one, and you have made a sack, and then it will go in, and not worry that most of the drop will run down your cheek. This doesn’t mean you have missed, because most of the drop can’t be held in the eye anyway. If your eye feels wet, it didn’t bounce off, it got in, and that’s enough. Then, just let your eye close gently for two or three minutes afterwards, because it is the pumping and squeezing that gets it to go down the nasal lacrimal duct into your nose. People who try to put their finger over the punctum, it just doesn’t work, and it isn’t necessary. Thom Zimmerman, I think now, who studied this and who is convinced about it, says you do just about as well by letting your eyes fall shut with the force of gravity. But do be sure to wait, as was pointed out very well in one of the lectures, at least we tell them five minutes, a couple of songs on the radio, whatever that is, if they are using more than one drug. I do like the idea, as brought up by Eve, of things like Cosopt and other drugs that are coming in combination where you are not going to have to worry about washing one drug out with another. I think those are the things that are worth telling people to do. And also, set up in your office to make sure that, if they don’t come back, if they miss a visit, you have some mechanism of noticing this and notifying them. My dentist does this, and it helps a whole lot, because I would probably be non-compliant half the time with my visits.

Dr Nussdorf: This meeting has brought up a number of questions about what we should be doing in our general eye clinic setting. You have a general ophthalmologist who doesn’t have prescreened patients sent to him. What is the best way to identify a glaucoma patient if you can’t screen them on the basis of intraocular pressure, a cup or even a normal visual field in a suspect? What do you use?

Dr Quigley: I assume that everybody in general practice has a perimeter. Since the older Humphrey perimeters are very unlikely to continue to be serviced, you are going to be forced to buy something new. I think that, in order to take care of most glaucoma patients, you are going to want to have an instrument that can perform SITA visual field testing. SITA-fast, even in someone who hasn’t done a field before, takes four minutes or less per eye. So, what I would urge you to do in general practice is that anyone with a risk factor should get a SITA-fast visual field

test in each eye along with your dilated examination of the disc. I wager that, if you do that, you are going to miss less than 5-10% of those who have early glaucoma.

At the present time, I can’t tell you that there is a test worth doing on every patient who comes to see you. The frequency doubling technology is good, but you would have to buy that separate free-standing piece of equipment. Whether they will produce one that is less expensive is problematic. At the moment we are trying to determine whether or not we can produce one that is less expensive and is simply head-mounted. I would think that, if there is a risk factor of any kind, a SITA-fast visual field should be added to your exam. The problem there is that you would probably have to define that the patient is a glaucoma suspect after a dilated exam and bring them back on another day for a field.

Dr Palmberg: Since I am very handy with it, I love the Zeiss gonioprism. If I were in general practice, I would pop it on everyone and take a look at their angle and nerve. You have a stereoscopic magnified view and you are not going to miss important glaucoma if you have looked at the nerve and at the angle.

Dr Quigley: We might ask, what is a risk factor for glaucoma? That is a family member that has been affected. What do you think are the chances of an African American over the age of 65 having glaucoma? It is about one in four. So you ought to be doing field testing on a large number of these persons. If there is an ocular hypertensive situation, if the disc is suspicious, and what is the cup-to-disc ratio that should knee-jerk a field test? In the population of the USA, a cup of 0.7 is extremely unusual. Only 2.5% of people have a cup as big as 0.7. I think all 0.7 and greater cups ought to have a field test as a way of not missing glaucoma. This doesn’t mean that we aren’t missing glaucoma. It doesn’t mean that there aren’t suspicious discs with notches that only have a total cup to disc ratio of 0.5, and those should also have a field test.

Now having said they should get a SITA-fast field test, 50% of initial field tests are unreliable. So you are actually buying them into two field tests a lot of the time. If they can do a normal field test, great. It is nearly impossible to do a normal field test the first time. So, if someone does that, you can believe it; it’s real. But, if their test is abnormal the first time, smile and say, “Well, you know that test, I’ll bet it was a little tricky to do, even the three-minute version. We are going to bring you back.” Now, if the patient is terribly anxious, you are going to bring her back next week, because you don’t want her staying up every night for the next six months waiting to find out if she has glaucoma. But, if the patient is not particularly worried about it and says, “Gee, doctor, I am really busy. I’ll come back in six months and we will do it then”, that’s fine, as long as it gets done.

Dr Nussdorf: Going back to the patient with Sturge-Weber and placing a seton in the eye, there was a question about lysing or pulling the ripcord and having a period of hypotony afterwards, which you have told us is important to guard against.

Dr Palmberg: If the pressure is particularly high, such as 40 or 50, and you have a Sturge-Weber with a large hemangioma, those are eyes that I really do favor these

days going in with a Baerveldt, and the minute I pull a 23-gauge needle out, I push a ligated tube in. It’s ligated with Vicryl and it is going to be three to five weeks before it opens. I don’t pull any cords or anything. By three to five weeks, you have a pretty good cocoon of tissue out around that plate. At that time, when the tube opens, the pressure doesn’t go to zero. If you do pull a cord, the first time you can measure with a Tono-Pen within a minute or so, you will find pressures of something like 8 to 10. So I don’t think it is as severe as if you were doing a filtering procedure. I have not yet seen someone with Sturge-Weber have one of these exudative detachments at that time. But is always going to be a concern. The same thing with nanophthalmos and people who have increased episcleral venous pressure.

Dr Quigley: I have seen a lot more folks with very prominent episcleral blood vessels, big ones, not pulsatile, not arterialized, not CC fistula, but simply prominent episcleral vessels and moderately high eye pressures, and they have pretty recalcitrant glaucoma. So, when somebody has very prominent blood vessels on the episclera, think about the possibility of glaucoma.

Dr Nussdorf: Do you think the studies concerning the genetics of glaucoma will lead to a vast improvement in diagnosis and eventual treatment?

Dr Palmberg: I sure do. Paul Nepra in Chicago, with whom we collaborated, did some work and found a biochemical defect that seems to be present in 60% of primary open-angle glaucoma. This could be something secondary and we will have to see where it leads. But, if we know who is at risk, if we knew the biochemical defect, and were able to detect genes and clone genes, I think this would be a great improvement. Perhaps these discoveries will lead to some ability to modify the trabecular meshwork by inserting a gene in the anterior chamber, which Don Gudenz did years ago in rabbits and now Paul Kaufman has been able to duplicate. I think we ought at least to be able to do things in the front of the eye genetically within 10 years. It will take more clever people to try to correct some problems at the back of the eye.

Harry may very well be right, that we will have pills, and once we have made the genetic diagnosis and know the problem, we will be able to target some systemic therapy for that person. So, yes, I have a great deal of optimism. I am a very optimistic person, I am very optimistic that we will be treating glaucoma differently in 10-20 years from now. We will be far more successful and people will look back and say, “Gee, I used to do it that way”.

Dr Quigley: I’m spending a lot of time right now attempting to do gene therapy in experimental glaucoma models, and those who have done this in a variety of diseases outside ophthalmology have not been terribly successful yet. There have been some real disasters. It is probably going to be more challenging than anyone thinks. As Paul says, it may be that the most important genetic information we get is diagnostic. If you know that one of two or three mutations in three or four different loci throughout the genome are more often associated with glaucoma, when you find the 31-year-old Japanese with the glaucoma, you might find out if he has one of those mutations and then look for it in his family members. Even if his two kids, aged 11 and 8, don’t have risk factors for glaucoma right now, if they

are carrying that mutation, it provides you with information to protect them better in the long term. I think the first thing we are going to find useful from genetic studies is diagnostic information for who is at risk for disease. We have not yet been very successful, though we have implanted genes into retinal ganglion cells in the rat eye, genes that should be neuroprotective, and that experiment will be analyzed in about 6 weeks. There is no question that gene insertion can be done. The question is, are we going to be doing it, is it going to be practical, and you can’t guess like that with research.

Dr Nussdorf: I want to thank our quest speakers for a wonderful morning discussion, and I am sorry to have to bring this session to end.