Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy. Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study. Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: comparison with systemic corticosteroids alone. Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration. Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy. Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer. Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients. A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation.
To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy.
                Single-blind randomised prospective study.
                Regional hospital, Hong Kong.
                Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003.
                NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans.
                The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy.
                A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity. Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs. The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation.
                In a double-blind randomised clinical trial, 30 patients with moderately severe Graves' orbitopathy had radiotherapy (20 Gy in ten fractions), and 30 were assigned sham-irradiation (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, such as eyelid aperture, proptosis, eye movements, subjective eye score, and clinical-activity score at 24 weeks.
                The qualitative treatment outcome was successful in 18 of 30 (60%) irradiated patients versus nine of 29 (31%) sham-irradiated patients at week 24 (relative risk [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. Quantitatively, elevation improved significantly in the radiotherapy group, whereas all other variables remained unchanged. The field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after sham-irradiation. Nevertheless, only 25% of the irradiated patients were spared from additional strabismus surgery.
                In these patients with moderately severe Graves' orbitopathy, radiotherapy should be used only to treat motility impairment. The effects of different methods of treatment of Graves' ophthalmopathy were evaluated in a series of 48 patients. Thirty-six patients were given combined treatment with orbital cobalt irradiation and systemic 6 alpha-methylprednisolone (methylprednisolone). Included in this group were 12 of 24 consecutive patients who were randomly assigned to either combined therapy or systemic methylprednisolone alone. The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index) and clinical assessment. Of the 36 patients treated by combined therapy, 12 (33%) showed excellent responses, 14 (39%) showed good responses, 9 (25%) showed slight responses, and 1 (3%) had no response. Treatment was more effective for soft tissue involvement, newly developed ophthalmoplegia, and optic neuropathy, while proptosis and longstanding ophthalmoplegia were less responsive. There was an inverse relationship between the duration of ophthalmopathy and the efficacy of treatment, more favorable results being observed when symptoms had been present for less than 2 yr. Treatment with systemic methylprednisolone alone was also effective, but, in general, responses were less satisfactory; 4 of the 12 patients of this group (33%) had good responses, 6 (50%) had slight responses, and 2 (17%) had no response. The results obtained in the 24 patients randomly assigned to combined therapy or steroid treatment alone were compared by evaluating changes in the ophthalmopathy index. Mean initial ophthalmopathy indices (6.4 vs. 6.2, respectively) showed no significant differences between the 2 groups, whereas the mean decrease in the group receiving combined therapy (4.8) was significantly greater (P less than 0.05) than that in the other group (3.2). In conclusion, the present study indicates that both orbital cobalt irradiation combined with systemic methylprednisolone treatment and systemic methylprednisolone therapy alone are valuable methods of treatment for Graves' ophthalmopathy, but the combined therapy proved to be more effective. To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study.
                Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment?
                Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation.
                Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group. Corticosteroids are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, we did a double-blind randomised trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Mean elevation in responders to radiotherapy increased from 18.5 degrees (95% CI 14.8-22.2) at baseline to 21.8 degrees (18.6-25.0) at week twenty-four (p = 0.003), but did not change in prednisone responders. Side-effects were more frequent and severe during prednisone than during radiotherapy. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice. The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M. To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients. The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD.
                Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion.
                At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P = 0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at least 12 months (P = 0.5, log rank test). No side effects were observed.
                Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited.
This review found that orbital radiotherapy is more effective than sham radiotherapy for the treatment of mild-to-moderate thyroid eye disease. In a single trial no difference between radiotherapy and steroid monotherapy was found. A meta-analysis of our secondary outcome of disease severity was not possible but results from individual trials suggest a better outcome with combination treatment with steroids versus steroids alone. No significant changes in quality-of-life scores following treatment with radiotherapy versus alternative treatments were found. Short-term adverse events related to radiotherapy that were reported were local and mild but long-term data were lacking and development of retinal changes following radiotherapy was not reported on.