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2 invited Radiotherapy for benign ocular diseases
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Thursday, 1 April 2004 Symposium/Proffered Papers Disorders of the eye 2 invited Radiotherapy for benign ocular diseases
M. Mourits UMC Utrecht, Utrecht, The Netherlands Background: Radiotherapy (RT) is applied in patients with benign and malignant ocular and orbital diseases such as Graves' orbitopathy, orbital meningioma and non-Hodgkin lymphoma. Knowledge of the effects of RT in patients with benign eye disease has been anecdotic or retrospective and therefore controversy exists about the efficacy and safety of RT in this group of patients. Method: At the UMC Utrecht, NL, we therefore, have conducted two prospective, randomised placebo-controlled studies to assess safety and efficacy of RT in patients with benign eye disease, e.g. 1 with Graves' orbitopathy and 2 with a pterygium. The results of radiotherapy as an adjuvant treatment in patients with a pterygium operated by the baresclera technique will be discussed in detail by Dr I.M. JQrgenliemk-Schulz in this symposium. Regarding our Graves' orbitopathy (GO study: 30 patients with moderately severe GO had RT (20 Gy in ten fractions) and 30 were assigned shamirradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables at 24 weeks. Results: The qualitative treatment outcome for GO was successful in 60% of irradiated patients versus 31% shamirradiated patients (RR=1.9+95%CI 1.0-3.6, p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Although the field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after shamirradiation, only 25% of the irradiated patients were spared from additional strabismus surgery. In the pterygium study the successful outcome after irradiation was significantly higher than after sham-irradiation. Serious side-effects have not been assessed in either of these studies.
Conclusions 1. In patients with moderately severe GO the effects of RT are of little clinical significance. 2. Additional irradiation after bare-sclera pterygium removal lowers the chance of recurrence. 3 invited Graves ophthalmopathy - Approaching targeted therapy
D. O'Shea ~ T.J. Cawood, P. Moriart7 ~St Vincent's University HospitaL Consu/tant Endocrino/ogist, Dublin 4, ~re~and 2St. Vincent's University Hospital, Dept. of Endocrinology, Dublin 4, Ireland 3The Royal Victoria Eye & Ear Hospital Dublin 2, Ireland Current treatment of thyroid eye disease (TED) is inadequate, consisting of high dose steroids, orbital radiotherapy, and decompressive surgery. Steroids have an adverse side effect profile, but do reduce disease severity. Orbital radiotherapy is controversial with the debate centered around whether TED improves as a result of the radiotherapy, or improves as part of
the natural course of the disease. Estimates of the proportion of patients who improve spontaneously are hard to find but a recent study which followed 81 patients, it was found that 47% improved spontaneous without treatment. Any effect of radiotherapy would have to be in addition to this spontaneous effect. Of the 34 trials of radiotherapy for TED that these authors can find only 3 are placebo-controlled studies. These demonstrate either no difference to control, or a small and clinically insignificant change in up-gaze (+4.9 degrees) or in proptosis (-0.7mm). With the possible side effects of cataracts and radiation retinopathy the use of radiotherapy for TED is likely to diminish in this evidencebased era. Surgery is only indicated for more severe disease, either when the disease is sight-threatening and unresponsive to other treatment modalities, or for functional and cosmetic reasons once the disease has 'burnt out'. Research into TED is hindered by the lack of access to retro-orbital surgical specimens from early in the disease process. Despite this, it is apparent that cytokines are involved in TED, particularly in the early stages of the disease. IL-1 has been shown to stimulate retro-orbital fibroblasts to produce glycosaminoglycan in vitro, and this effect can be blocked by antagonists of IL-I. Agents which modulate the effects of certain cytokines, if given early in the course of the disease, may represent a future therapeutic strategy for TED. 4 oral Prevention of pterygium recurrence by post-operative singledose beta-irradiation: a prospective randomised clinical double-blind trial
I.-M. JEtr.qenliemk-Schulz7, L.J.C. Hartman2, J.M. Roesink 1, R.J.H.A. Tersteeg ~, I. van der Twee3, H.B. Kal 7, M.P. Mourits2, H.K. Wyrdeman 7 1UMC Utrecht, Department of radiation oncology, Utrecht, The Netherlands 2UMC Utrecht, Department of Ophthalmology, Utrecht, The Netherlands 3Utrecht University, Centre for Biostatistics, Utrecht, The Netherlands Purpose: pterygium is a benign disease of the supporting orbital tissue that can cause impairment of visual function. Depending on the technique that is used for surgery, recurrence is described in up to 70% of the cases; reason to combine initial treatment with radio- or chemotherapy. In order to affirm the effectiveness and complication rate of post-operative single-dose beta-irradiation with Strontium 90 (9°Sr) in case of primary pterygium, we initiated a clinical trial. Methods and materials: the described trial was designed as a prospective randomised multi-centre double-blind study. Surgery was performed in all cases according to the bare sclera technique. Ninety-one patients with 96 pterygia were postoperatively randomised to either beta-irradiation or shamirradiation. In case of beta-irradiation a 9°Sr eye applicator was used to deliver 2500 cGy to the sclera surface with a dose rate between 200 and 250 cGy/minute. Sham-irradiation was given using the same type of applicator without the 9°Sr layer. After treatment, both an ophthalmologist and radiation oncologist performed follow-up. Accumulating data were analysed groupsequentially. Results: between February 1998 and September 2002 96 eyes with primary pterygium were operated on according to the trial protocol. Additional treatment was performed within 24 hours post-operatively. Ten patients were lost to follow-up resulting in 86 patients that could be analysed. In the 44 eyes, which were randomised to receive beta-irradiation we observed 3 relapses, compared to 28 recurrences in the 42 eyes that were sham
Thursday, 1 April 2004 Symposium/Proffered Papers Disorders of the eye 2 invited Radiotherapy for benign ocular diseases
M. Mourits UMC Utrecht, Utrecht, The Netherlands Background: Radiotherapy (RT) is applied in patients with benign and malignant ocular and orbital diseases such as Graves' orbitopathy, orbital meningioma and non-Hodgkin lymphoma. Knowledge of the effects of RT in patients with benign eye disease has been anecdotic or retrospective and therefore controversy exists about the efficacy and safety of RT in this group of patients. Method: At the UMC Utrecht, NL, we therefore, have conducted two prospective, randomised placebo-controlled studies to assess safety and efficacy of RT in patients with benign eye disease, e.g. 1 with Graves' orbitopathy and 2 with a pterygium. The results of radiotherapy as an adjuvant treatment in patients with a pterygium operated by the baresclera technique will be discussed in detail by Dr I.M. JQrgenliemk-Schulz in this symposium. Regarding our Graves' orbitopathy (GO study: 30 patients with moderately severe GO had RT (20 Gy in ten fractions) and 30 were assigned shamirradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables at 24 weeks. Results: The qualitative treatment outcome for GO was successful in 60% of irradiated patients versus 31% shamirradiated patients (RR=1.9+95%CI 1.0-3.6, p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Although the field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after shamirradiation, only 25% of the irradiated patients were spared from additional strabismus surgery. In the pterygium study the successful outcome after irradiation was significantly higher than after sham-irradiation. Serious side-effects have not been assessed in either of these studies.
Conclusions 1. In patients with moderately severe GO the effects of RT are of little clinical significance. 2. Additional irradiation after bare-sclera pterygium removal lowers the chance of recurrence. 3 invited Graves ophthalmopathy - Approaching targeted therapy
D. O'Shea ~ T.J. Cawood, P. Moriart7 ~St Vincent's University HospitaL Consu/tant Endocrino/ogist, Dublin 4, ~re~and 2St. Vincent's University Hospital, Dept. of Endocrinology, Dublin 4, Ireland 3The Royal Victoria Eye & Ear Hospital Dublin 2, Ireland Current treatment of thyroid eye disease (TED) is inadequate, consisting of high dose steroids, orbital radiotherapy, and decompressive surgery. Steroids have an adverse side effect profile, but do reduce disease severity. Orbital radiotherapy is controversial with the debate centered around whether TED improves as a result of the radiotherapy, or improves as part of
the natural course of the disease. Estimates of the proportion of patients who improve spontaneously are hard to find but a recent study which followed 81 patients, it was found that 47% improved spontaneous without treatment. Any effect of radiotherapy would have to be in addition to this spontaneous effect. Of the 34 trials of radiotherapy for TED that these authors can find only 3 are placebo-controlled studies. These demonstrate either no difference to control, or a small and clinically insignificant change in up-gaze (+4.9 degrees) or in proptosis (-0.7mm). With the possible side effects of cataracts and radiation retinopathy the use of radiotherapy for TED is likely to diminish in this evidencebased era. Surgery is only indicated for more severe disease, either when the disease is sight-threatening and unresponsive to other treatment modalities, or for functional and cosmetic reasons once the disease has 'burnt out'. Research into TED is hindered by the lack of access to retro-orbital surgical specimens from early in the disease process. Despite this, it is apparent that cytokines are involved in TED, particularly in the early stages of the disease. IL-1 has been shown to stimulate retro-orbital fibroblasts to produce glycosaminoglycan in vitro, and this effect can be blocked by antagonists of IL-I. Agents which modulate the effects of certain cytokines, if given early in the course of the disease, may represent a future therapeutic strategy for TED. 4 oral Prevention of pterygium recurrence by post-operative singledose beta-irradiation: a prospective randomised clinical double-blind trial
I.-M. JEtr.qenliemk-Schulz7, L.J.C. Hartman2, J.M. Roesink 1, R.J.H.A. Tersteeg ~, I. van der Twee3, H.B. Kal 7, M.P. Mourits2, H.K. Wyrdeman 7 1UMC Utrecht, Department of radiation oncology, Utrecht, The Netherlands 2UMC Utrecht, Department of Ophthalmology, Utrecht, The Netherlands 3Utrecht University, Centre for Biostatistics, Utrecht, The Netherlands Purpose: pterygium is a benign disease of the supporting orbital tissue that can cause impairment of visual function. Depending on the technique that is used for surgery, recurrence is described in up to 70% of the cases; reason to combine initial treatment with radio- or chemotherapy. In order to affirm the effectiveness and complication rate of post-operative single-dose beta-irradiation with Strontium 90 (9°Sr) in case of primary pterygium, we initiated a clinical trial. Methods and materials: the described trial was designed as a prospective randomised multi-centre double-blind study. Surgery was performed in all cases according to the bare sclera technique. Ninety-one patients with 96 pterygia were postoperatively randomised to either beta-irradiation or shamirradiation. In case of beta-irradiation a 9°Sr eye applicator was used to deliver 2500 cGy to the sclera surface with a dose rate between 200 and 250 cGy/minute. Sham-irradiation was given using the same type of applicator without the 9°Sr layer. After treatment, both an ophthalmologist and radiation oncologist performed follow-up. Accumulating data were analysed groupsequentially. Results: between February 1998 and September 2002 96 eyes with primary pterygium were operated on according to the trial protocol. Additional treatment was performed within 24 hours post-operatively. Ten patients were lost to follow-up resulting in 86 patients that could be analysed. In the 44 eyes, which were randomised to receive beta-irradiation we observed 3 relapses, compared to 28 recurrences in the 42 eyes that were sham