patient is receiving radiation. He has had good results with this method. If there is a poor response to high-dose steroids, he is inclined to be mechanical about the treatment.

Question 4 (from M. Mourits)

‘‘From what I have heard today, I think we agree on many points nowadays. We agree about management of patients with mild orbitopathy. We generally agree about management of patients with vision-threatening disease. We agree about surgical approaches, although there are numerous different approaches. As long as they work, we do not mind. But the burning question is what do we do with active, moderately severe Graves’ orbitopathy? I have not had an answer to that question yet. In these times of evidence-based medicine, we have demonstrated in two independent institutions that the efficacy of radiotherapy is very limited if at all present. Oral prednisone and IV prednisone, of which everybody is talking now, have never been tested in a controlled study. So my question is how do I treat these patients, which is the largest group of patients I see?’’

Answer

Dr. Rootman’s response was twofold. Firstly, the specialist needs to see the patients at an earlier stage of their disease to try and prevent it. Secondly, a more active approach to these studies needs to be taken to determine how to proceed with, or set guidelines for, these studies.

In return, Dr. Rootman asked that the audience consider the following question: why are orbital specialists discussing single-modality therapy for an ‘‘immunologically based disease’’ when virtually every other discipline has moved to multimodality therapies or sequential therapies based upon the biology of the disease process? Under present circumstances, there does not seem to be clear evidence agreed upon by all for the treatment of moderate to severe cases. He felt that the studies or reports done so far were anecdotal and that the prospective, multitherapy studies needed to be done. This seemed to be the path for the future.

Question 5 (from F. Buffam)

‘‘Does anybody leave patients on moderate dose steroids for months?’’

Answer

Dr. Rootman noted that he has had a bad experience with patients on long-term oral steroids, with side effects that ranged from perianal abscesses to psychotic episodes. He felt that the chronic use of oral steroids was really disappointing. He agreed with previous comments that there is much frustration in choosing the appropriate treatment but felt that oral administration was the worse way of using steroids.

Question 6 (from F. Buffam)

‘‘What is the longest time period to leave a patient on steroids?’’

Answer

Dr. Kennerdell indicated that, in his practice, the longest time he has left a patient on steroids was 3 months. He was very disappointed with oral steroids and leaves patients on them only as long as he absolutely has to use them; generally, he prefers their use in an acute manner only. It is more effective to find out what needs to be dealt with, whether this patient will respond or not, then turn to another modality.

Dr. Gorman commented that the course of treatment that one offers a patient is a negotiation between the patient on one hand explaining their discomforts and the physician on the other hand dispensing from a limited variety of therapies. Many times, it is a question for the patient of ‘‘I can put up with what I have wrong today but can you tell me when it will end?’’ If the patient is on the plateau phase of the illness, it is difficult to tell them when it will end but a general idea of when symptoms tend to ameliorate can be conveyed.

Dr. Rootman then noted that one could be more effective in prognosticating and allowing patients to know what is going to happen with their disease, which can be an enormous

relief to a patient who has what used to be called ‘‘noninfiltrative disease.’’ For example, a 30-year-old patient who is a nonsmoker has good prognostic factors and therefore can be told that their disease will most likely not progress or worsen.

Dr. Kazim supported Dr. Rootman’s remarks on giving patients a general, good, broad outlook at the initial visit. For patients who see him early in the course of their disease without a long history before they arrive, he tends to see them again in a month. If the patients proceed from not so bad to particularly bad over this 4-week period, it identifies for him those who will go through an acute congestive phase. This is generally a small number of patients but he prefers to identify them so that he can consider more aggressive intervention.

Dr. Wiersinga wished to comment on an earlier question, Question 4. He noted that much progress had been made over the last 10 years in this area, especially with carefully executed randomized trials, though research in Graves’ management does lag behind other fields in this respect. New trials to research interventions are indeed the way forward. A member of the audience commented earlier on his ‘‘quadruple intervention’’ approach, which is probably a good approach; however, there are so many biases involved in this particular disease that Dr. Wiersinga could not accept his results without support from a prospective randomized clinical trial.

In order to make real progress, studies have to be completed faster and these studies should be multicenter. In Europe, the European Group on Graves’ Ophthalmopathy (EUGOGO) was organized for this purpose, with participation from nine European centers. The main difficulty the group now faces is reaching inter-observer agreement, and once that is achieved, multicenter trials can begin. Then, more progress can be achieved in a shorter period of time.

Question 7 (from P. Dolman)

‘‘I am a little confused about the classification of mild, moderate and severe as different panelists describe it. I think some

panelists are saying that severe ophthalmopathy means there is optic neuropathy and in my mind, that is a separate category and has a different management strategy. I think some are saying that mild disease is what we would categorize as already quiescent; these patients have surgical problems with lid retraction, and perhaps proptosis and will need surgery for that. Therefore, I believe that if we are to discuss mild, moderate, and severe disease, we should really refer to inflammatory activity or progress or whatever term one wants to use to prove that something can be medically responsive. I still feel a bit muddy when the broad terms, moderate or severe, are applied to different aspects. Because of this, our group proposed the ‘‘VISA’’ (vision, inflammation, strabismus, and appearance) classification to define the medical features of inflammation.’’

Answer

Dr. Rootman responded by noting that he was the one who initially posed the question to the panel and that it was in the context of active, moderate disease. He had hoped the panel would divide management into the categories of what was going to be done for soft tissue components (inflammation), strabismus, and appearance. He noted that optic neuropathy patients are a different category, since they can present with variable activity or soft-tissue or inflammatory features associated with their optic neuropathy and will need to be managed on an individual basis. The use of the categories proposed by the VISA classification allowed for defining the character of the disease and appropriate management.