Questions and Answers

Questions and Answers

Presiding Physician: Jill Koury, MD

Panel: Harry Quigley, MD

Eve Higginbotham, MD

Paul Palmberg, MD, PhD

Richard Mackool, MD

Peng Khaw, MD, PhD

Dr Koury: Is there a study that compares the relationship between age and cup to disc ratio?

Dr Quigley: If you look at population data where the cup to disc ratio is rated against age, the cup to disc ratio gets slightly larger in cross-sectional data, and if you interpret that as being appropriate for an individual who would age over a 40 year span, then you lose a few ganglion cells every year. The best estimate is that you and I lose between 20 and 25% of our ganglion cells during our lifetime.

Dr Koury: Do you use Mitomycin for all tubes or just tubes in children?

Dr Khaw: I use Mitomycin for all tubes, because I need to get a low target pressure and I use staged procedures to get the pressure right down to the low teens – all tubes.

Dr Koury: Dr Khaw, have you done comparisons between 5FU and Mitomycin in your institution? What are the results?

Dr Khaw: We haven’t done a formal randomized study, but there are two randomized studies and interestingly the randomized studies are finding it very hard to show the difference between Mitomycin and 5FU. The proviso of that statement is that the attendings were allowed to intervene postoperatively and therefore, inevitably I am sure what they did was by intervening, needling, and adjusting sutures, they were probably able to make the two groups closer together. Certainly, from the randomized point of view, it is very hard to show a difference between Mi- tomycin-C and 5-FU. Clinically, Mitomycin gives you a lower pressure, but you do pay a price, because it does lead to more problems with hypotony.

Dr Palmberg: I did consecutive series. It is not quite the same thing, but they looked identical (this was with five injections of 5-fluorouracil in the first two weeks, not the sponge) and we found an average pressure of 10 after 10 to 11 years with Mitomycin or 5-FU. It made no difference in pressure control or failure, and we didn’t have

Eye on the Bayou, New Concepts in Glaucoma, Cataract and Neuro-Ophthalmology, pp. 215–220 Transactions of the 54th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, February 18-20, 2005

edited by Jonathan D. Nussdorf

© 2006 Kugler Publications, The Hague, The Netherlands

that much difference in complications either when we used five injections of 5-FU compared to Mitomycin – a little bit more leaks, a little more infection with the Mitomycin, but not any more hypotony. I think we got more attuned to thinking about hypotony and what to do about it as years went on, and that gave the impression that Mitomycin was causing hypotony. 5-FU can certain do it too, if you don’t have proper scleral resistance.

Dr Quigley: We have six glaucoma specialists at Wilmer and our fellow is about to do a little exogesis in which she has watched all of us operate, and she is going to give us a little talk and say that you guys aren’t doing the same operation. There is not one of you that is doing what the other one is. When you begin talking about comparing across clinical trials trabeculectomy methodology, as Peng said, there is a lot of stuff that goes on postoperatively with suture-lysis or releasables, with how you manage the steroid, with what you are doing with needling and other stuff, that is very hard to control in one series versus another; it is even very hard to control within one series. This is one variable among a very large number of variables in glaucoma surgery. In addition, the outcome measures are not necessarily the same in studies as you compare them. I certainly agree with what Peng says – you pay a price for Mitomycin, but it’s worth it a lot of the time.

Dr Palmberg: I think how you apply these drugs makes a great deal of difference. When you used 5-FU, what was that sponge like? Did it force fluid into the tissue, or was it just a thin thing laid there with the conjunctiva on top? It is quite confusing to me about 5-FU with sponges. There are four randomized trials now – two in Latin America that showed no benefit. You didn’t show any difference in pressure, and yet the one Kuldev will tell us about perhaps with 5-FU versus Mitomycin, the average pressure was 10 and 11, not 13. In some studies it looks like 5-FU and a sponge is very effective and in others it doesn’t. I wonder if it’s how 5-FU is applied. We know it makes a tremendous difference in Mitomycin how the sponge is put in, whether it is a full sponge shoved in or it’s a thin sponge and you just lay tissue on top, how much does it penetrate, time, concentration. The method of using Mitomycin or 5-FU, as you say, what one person does could be quite different from what other people are doing, and the results will reflect the difference.

Dr Koury: One related question to Dr Khaw, do you now use 5-FU in post-op care, or only at surgery?

Dr Khaw: I do use 5-FU in post-op care. The evidence for using post-op injections of Mitomycin or 5-FU, is not fantastic. A Cochran analysis of the literature suggests that if you give less than three injections of 5-FU, you can’t find a trend that the post-op injections make much difference in trabeculectomy outcome. Having said that, I do use post-op 5-FU injections. If I feel the bleb is failing and it showing the signs, the pressure is rising or there is injection in the eye, then I use subconjunctival injections of 5-fluorouracil.

Dr Quigley: And sacrificing a goat helps.

Dr Koury: What patient characteristics would make you more likely to choose

5-FU instead of Mitomycin during primary trabeculectomy, i.e., age, specific risk factors, and so on?

Dr Khaw: I obviously see very high risk patients, so generally I use much more Mitomycin than 5-fluorauracil. I think Paul may disagree on this, but certainly in general use out there if you have an elderly patient, which accounts for a great many of our patients, who have few risk factors, who are not advanced, then 5- fluoruacil is appropriate for a lot of our patients.

Dr Koury: Dr Khaw, one follow-up question, what kind of sponges were used for the 5-FU sponge study?

Dr Khaw: The sponges that were used in the 5-FU study were methylcellulose sponges. Having said that, we now all use polyvinyl alcohol sponges. The reason for that is that we and others looked at this and you just don’t get fragmentation with the polyvinyl alcohol sponges. I am sure all of you have experience with using the other sponges; you get all sorts of bits all over the place. So we now use polyvinyl alcohol sponges.

Dr Palmberg: For Mitomycin, I just cut off the side of a Weck-Cel sponge and it makes a piece about 6 x 4 mm and very thin and we have gotten quite good results and thank goodness, only one late leak and so far no infections in five years. That was an incredible change from six percent. Before putting any fluid on it we cut the sponge, then we apply the antimetabolite.

Dr Higginbotham: I certainly would consider using topical 5-FU in a patient that is a high myope and a patient that is younger than 45 years old, just because of the fact that there is a greater likelihood of having hypotony occur following the use of Mitomycin in those instances.

Dr Koury: There are very positive reports from India of a large series of congenital glaucoma cases in which combined trabeculectomy plus trabeculotomies were done. Dr Khaw, do you combine these two procedures, and would you use antimetabolites in those cases?

Dr Khaw: This is comes from Anil K. Mandal’s very large series. He is a fantastic surgeon and he has carried out really the world’s biggest series of these trabeculotomies/trabeculectomies. I have done trabeculectomy/ trabeculotomy, and I find them tricky. The way we do trabeculectomy now relies on very tight control of the scleral flap and how fluid flows. The problem is when you do a trabeculotomy at the same time you do lose that control. So personally I do not perform these combined procedures. But I have to say his results are truly remarkable. I think if you are good at it and you get good results, then I would say continue it.

Dr Koury: Dr Higginbotham, how can we join with our optometric colleagues for more effective outreach to the underserved?

Dr Higginbotham: That’s an interesting question. In my spare time I chair the Planning Committee for the National Eye Health Education Program, which is the educa-

tional arm for the National Eye Institute, to coordinate the activities of about seventy organizations that are out there doing the work of increasing awareness about eye disease. The Academy of Ophthalmology is one of the partners as well as the American Academy of Optometry. I invite all of you to become more involved. Because yes, they are more engaged and whatever you can do in your local communities to be more involved is the first step. Certainly, people that are out there doing the glaucoma screenings or vision screenings are invariably optometrists, but there is no reason why we can’t see more ophthalmologists.

Dr Koury: Thank you Dr Higginbotham. Dr Mackool, with bimanual phaco, is there an increase in wound burn since the phaco tip has no sleeve?

Dr Mackool: Well, it depends on whom you talk to. The real truth is, yes, there have been some wound burns out there. Nobody knows the incidence. I think the wound burns occurred with a 1.1 mm incision. But not when using 1.5 mm incisions, because they leaked and the wound burn issue went away.

Dr Koury: Dr Khaw, how do you manage Sturge-Weber glaucoma in very young children? What is your procedure of choice?

Dr Khaw: Obviously, Sturge-Weber is one of the conditions which everybody fears greatly. Almost all these children who have glaucoma have a choroidal hemangioma, which obviously is a risk when you are doing penetrating surgery. One of the fellows has evaluated our experience with fifty-five patients with Sturge-Weber glaucoma. Initially, we either perform an angle surgery or a trabeculectomy. Angle surgery works well for about a year and then it begins to fail. So angle surgery is a good short-term procedure if you feel that drainage surgery isn’t good. We have been comparing two other groups – one who had beta radiation, which was our standard, and the new lot who have had Mitomycin. If you consider an IOP of less than 21 a success, then Mitomycin trabeculectomy provides an 85% success rate over two years, and if you use beta radiation, the success rate is only about 70%. So our standard treatment, if there is no contraindication, is a Mitomycin trabeculectomy with the large surface area treatment.

Dr Quigley: I’d agree with trabeculectomy. I think your biggest fear is not bleeding of the episcleral hemangioma because while it looks like heck as you start the surgery, it actually doesn’t bleed that much more than the episclera normally bleeds. Your real concern is choroidal expansion. Because with a low intraocular pressure, the choroid tends to expand and you get a very large choroidal so-called detachment. That is now going to be the wrong term for it, but that’s okay. They can maintain this choroidal detachment for an extended period of time, which sounds good for the pressure but is bad for the lens.

Dr Palmberg: We have gone to using Baerveldts in all of these kids and getting away from filtering surgery partly because with HMO’s and managed care in our area it was very difficult to follow blebs in children. They went from pediatrician to pediatrician and they all decided they could treat that red eye when it occurred. It is difficult to examine these kids. Certainly you can’t adjust your filter by lasering stitches or something afterwards, so we have had very good results. Also, you don’t

have to decompress the eye at the time of surgery and get those retinal effusions or whatever you want to think of them in those cases.

Dr George Ellis: I have a question about pediatric glaucoma. I know that there is a wealth of experience up here, although Dr Khaw did give the lecture on congenital glaucoma. Maybe the other glaucomologists could jump in on this as well. What is your operation of choice for an African American baby born with cloudy corneas and diameters of 12 and 13 mm with intraocular pressures of 30 and 40 mmHg on Timoptic and Diamox at 10 mg/kg every six hours? What would be your initial procedure that you would want to do and how quickly would you do it and why?

Dr Quigley: George, how did you measure the pressure? What was the anesthesia and what was the machine you used?

Dr Ellis: Tono-Pen under Ketamine anesthesia.

Dr Higginbotham: Except for the buphthalmos, that describes a patient I recently had. We caught this patient just at three weeks of age. So the ocular enlargement hadn’t started yet. My choice at that moment was trabeculectomy/trabeculotomy. I always like to supplement it, particularly in those patients that do present with cloudy corneas and I am concerned about the long term issues. Invariably, the trabeculectomy doesn’t really give me a cystic bleb in this age group anyway, but I guess it gives me a little bit more comfort in case I am not happy with cannulating Schlemm’s canal on both sides. I generally would use trabeculectomy/trabeculotomy with Mitomycin C.

Dr Koury: Eve, when you do your trabeculotomy, do you use a trabeculotome or do you use a suture?

Dr Higginbotham: I use a trabeculotome.

Dr Quigley: Bilateral trabeculotomy at one sitting, and I think you give the angle surgery a chance. Success rate in that particular setting is probably fifty percent. You maybe going back to do another trabeculectomy later. Don’t center the thing right straight up at 12 o’clock, because it will interfere with the later trabeculectomy.

Dr Ellis: And how long do you give that angle surgery to work?

Dr Quigley: If it isn’t down at six weeks you are going to have to move. We would typically do an EUA early at a month to six weeks and see what the pressure has done. If the cornea clears, you already know what is going on.

Dr Ellis: If the cornea doesn’t clear, in which amblyopia is a big issue here, then you’d have to go in sooner.

Dr Palmberg: We really like to do Mary Lynch’s operation using Prolene suture passed 360 degrees around and get all the angle surgery done at once. We do this temporally so that you are doing almost nothing to the superior conjunctiva. Our

usual second choice would be to put in an inferonasal Baerveldt, which also saves superior conjunctiva or it could be put superotemporally.

Dr Khaw: We have had about five of these children over the last two years and we have used goniotomy in all of them and they seem to do okay. All of those five have pretty good pressures. We have had to strip their corneas with alcohol at the time, but that grows back after about three or four days. The advantage I have of using goniotomy is that you effectively have a virgin eye when it comes to doing any secondary procedure and you haven’t altered the conjunctiva.

Dr Ellis: The reason I asked is because the literature says that a child born with buphthalmos, cloudy corneas and a high intraocular pressure signifies that the anatomy of Schlemm’s canal is not well formed. I was curious as to why would a goniotomy work or why would trabeculotomy work.

Dr Khaw: I didn’t quite catch the age of presentation. The ones I am talking about are the ones who usually present at two or three months. Your child presented at birth?

Dr Ellis: Yes, the neonatologist noted in the ICU on day one and ophthalmologist examined on day two and transferred him to us on day three.

Dr Quigley: I am unfamiliar with any actual histology that shows that those children are different from kids who presented three months or six months or one year. I think you are having surgeons guessing what they think is true of Schlemm’s canal when they went in to operate. We actually don’t put the probe in Schlemm’s canal anyway; we put it in the scleral sulcus. So whether there is a Schlemm’s canal or not may or may not even be relevant.

Dr Palmberg: That is a very important point. If you get in there and can’t find Schlemm’s canal, just do what would be I guess a cyclodialysis kind of incision… Doug Anderson taught me to do this if I ran into that kind of case… and the corneas cleared and they did well. I do not understand the anatomy of what we fixed.

Dr Quigley: The trabeculotome probe is about three to four times larger than Schlemm’s canal. And Schlemm’s canal is discontinuous in most adults, it is probably discontinuous in children. So we are making false passages a lot of the time probably.