Reduction In Clinical Activity Score Research Articles

A retrospective study on the effectiveness of intensity modulated radiation therapy for thyroid associated ophthalmopathy at a single institute

Thyroid-associated ophthalmopathy (TAO) is a hallmark autoimmune condition, and the treatment of TAO requires a multidisciplinary approach. Radiation therapy (RT) is a viable treatment option for active TAO, IMRT is a more precise technology in radiation oncology. This study aims to evaluate the efficacy, feasibility, and safety of orbital intensity-modulated radiation therapy (IMRT) in the treatment of TAO. A single-center retrospective analysis was conducted, including patients diagnosed with moderate to severe active TAO at the Department of Radiation Oncology, Peking University Third Hospital, from October 2020 to October 2023, who had poor responses to corticosteroid treatment. These patients subsequently received IMRT treatment, followed by a period of follow-up and retrospective analysis. The study focused on the outcomes of treatment efficacy, safety, and acute toxic reactions induced by radiation therapy. Improvements in clinical activity score (CAS) at 4 and 12 months were considered as primary and secondary study endpoints, respectively, along with the incidence rate of adverse events. The median follow-up period was 12 months. The median follow-up time after radiation therapy was 12 months. There was no statistically significant difference in CAS between before and 4 months after radiation therapy (CAS: 5.53 ± 2.07 vs.4.68 ± 2.62; R squared: 0.21; 95% CI: − 1.01–0.02; P = 0.054). However, there was a significant reduction in CAS 12 months post-treatment compared to pre-treatment (CAS: 5.53 ± 2.07 vs. 3.06 ± 2.38; R squared: 0.66; 95% CI: 3.42 − 1.52; P < 0.001). The CAS showed a progressively decreasing trend at both 4 months and 12 months post-treatment. In the combined radiotherapy with glucocorticoid treatment group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 6.38 ± 2.00 vs. 3.88 ± 2.85; R squared: 0.66; 95% CI − 4.11 to 0.89; P = 0.008). In the radiotherapy alone group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 4.78 ± 1.92 vs. 2.33 ± 1.73; R squared: 0.66; 95% CI − 3.89 to 1.00; P = 0.005). A few patients experienced Grade I periorbital edema, conjunctival congestion, and dry eye syndrome, but no adverse events such as cataracts, radiation retinopathy, or radiation-induced optic neuropathy were observed by the end of the follow-up period. Orbital IMRT is an effective treatment modality for moderate to severe active TAO, demonstrating significant efficacy even in patients who had not achieved success with previous treatments such as corticosteroids. This retrospective study was approved by the Ethics Committee of Peking University Third Hospital. The permit number was M2024220 and data of registration was April I, 2024.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

FRI545 Durability Of Treatment Response With VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor, In Patients With Thyroid Eye Disease (TED): Phase 1/2 Clinical Study

Abstract Disclosure: R. Douglas: Consulting Fee; Self; Horizon Therapeutics, Viridian Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. S. Ugradar: Consulting Fee; Self; Viridian Therapeutics Inc. K. Cockerham: Advisory Board Member; Self; Viridian Therapeutics Inc., Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Speaker; Self; Horizon Therapeutics. R.E. Turbin: Advisory Board Member; Self; Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Stock Owner; Self; Viridian Therapeutics Inc. R. Tang: Consulting Fee; Self; Viridian Therapeutics Inc. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. N. Nijhawan: Research Investigator; Self; Viridian Therapeutics Inc. D.J. O’Shaughnessy: Employee; Self; Viridian Therapeutics Inc. R.M. Summerfelt: Employee; Self; Viridian Therapeutics Inc. A. She: Employee; Self; Viridian Therapeutics Inc. B. Katz: Employee; Self; Viridian Therapeutics Inc. Introduction: Clinical and preclinical evidence demonstrate IGF-1 receptor (IGF-1R) antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity, full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 double-masked RCT (NCT05176639) at 3, 10, or 20 mg/kg administered intravenously. Results from the first cohort of TED patients (10 mg/kg) are presented here. Methods: Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy through 12 weeks were assessed. Endpoints included overall responder rate (% of patients with ≥2 mm reduction in proptosis and ≥2 point reduction in CAS), proptosis responder rate (% of patients with ≥2 mm reduction), change from baseline in proptosis and CAS, proportion of patients with CAS decrease to 0 or 1, and diplopia resolution. Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, at 6 weeks, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Mean proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo). MRI analysis of proptosis, available for 4 of 6 drug-treated patients, confirmed proptosis improvement in each; MRI analysis showed slight worsening of proptosis in both placebo patients. CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo), with mean decreases of 4.3 (VRDN-001) and 1.5 (placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). Durability of response in the 5 VRDN-001 treatment responders at 6 weeks persisted through 12 weeks: 80% (4/5) maintained overall responder status and 80% (4/5) maintained proptosis responder status, with mean reduction in proptosis at week 12 of 2.2 mm for all 6 drug-treated patients; MRI analysis confirmed the maintained response for all 4 of the drug-treated patients for whom scans were available. Mean CAS reduction remained consistent (4.2 at Week 12 vs. 4.3 at Week 6) and 80% (4/5) maintained a CAS of 0 or 1. All 4 patients with baseline diplopia had diplopia resolution at Week 12. VRDN-001 was well-tolerated through 12 weeks. AEs were mostly mild, with no severe or serious AEs reported. Conclusions: Two infusions of 10 mg/kg VRDN-001 were well tolerated in this cohort of TED patients, and the rapid, clinically meaningful improvement across all efficacy measures by 6 weeks was sustained through 12 weeks. Further, these results were achieved with a lower dose and fewer treatments than in prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens. Presentation: Friday, June 16, 2023

Phase 1/2 Clinical Study of VRDN-001, A Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients with Thyroid Eye Disease (TED) (P3-9.001)

Phase 1/2 Clinical Study of VRDN-001, A Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients with Thyroid Eye Disease (TED) (P3-9.001)

Effects of Smoking on Outcomes of Thyroid Eye Disease Treated with Teprotumumab: A Retrospective Cohort Study.

Smoking has been demonstrated to worsen the disease process and conventional treatment outcomes of thyroid eye disease. However, the effects of smoking on outcomes of thyroid eye disease treated with the novel therapeutic teprotumumab are currently unknown. Our study compares response to teprotumumab treatment between smokers and non-smokers with thyroid eye disease. A single-center, retrospective cohort study was conducted. Inclusion criteria were patients diagnosed with thyroid eye disease who had started or completed therapy with teprotumumab at the time of our data collection. Main outcome measures included reduction in clinical activity score, diplopia, and proptosis. All smokers had type 2 thyroid eye disease prior to treatment and demonstrated less improvement in diplopia, proptosis, and overall clinical activity score compared to non-smokers with thyroid eye disease. There was no significant difference between smokers and non-smokers in baseline variables (sex, thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), number of infusions completed). Data analysis revealed a statistically significant difference in proptosis reduction between non-smokers and smokers. Smoking is a modifiable risk factor which portends a worse response to treatment of thyroid eye disease with teprotumumab.

Ocular surface and in vivo confocal microscopic findings in patients with active tyhroid eye disease treated with glucocorticoids.

To evaluate the effect of treatment with high-dose glucocorticoids (HDG) on ocular surface parameters and in vivo confocal microscopy (IVCM) findings in patients with active thyroid eye disease (TED). This study included 15 active TED patients treated with a cumulative HDG dose of 4.5g (500 mg and then 250 mg for 6 weeks each). Disease activity was assessed by the clinical activity score (CAS), Graves' Orbitopathy-specific Quality of Life (GO-QoL) questionnaire, ocular surface disease index (OSDI), tear break-up time(T-BUT), ocular surface staining and IVCM. The mean follow-up time was 48.6 months. The treatment resulted in a significant improvement in the T-BUT, ocular surface staining values. In comparison to the baseline, a notable reduction in CAS, OSDI and an increase in GO-QoL were seen after one year. IVCM showed a significant decrease in the number of dendritic cells, activated keratocytes, the degree of tortuosity, there was also a significant increase in the number of basal epithelial cells and total nerves over one-year period. All of those changes remained stable during the follow-up period. HDG treatment results in a sustained decrease in corneal inflammatory cells, an increase in tear film stability, and an improvement in disease symptoms and QoL scores for up to 4 years.

Monoclonal antibodies for the treatment of Graves' ophthalmopathy: A systematic review and meta-analysis.

The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ]). We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. Six (n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, P < 0.00001, I2 = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, P = 0.002, I2 = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, P = 0.02, I2 = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, P = 0.001, I2 = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, P = 0.03, I2 = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels. This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids.

Early Experience With the Clinical Use of Teprotumumab in a Heterogenous Thyroid Eye Disease Population.

To describe the clinical course in a heterogeneous series of subjects with thyroid eye disease (TED) treated with teprotumumab. Cross-sectional cohort study including patients with clinical diagnosis of TED who was treated with teprotumumab. The entire cohort was analyzed together and subsequently in clinical subgroups based on stage and grade of disease. Primary outcome measure was change in proptosis ≥2 mm. Secondary outcome measures included change in clinical activity score (CAS), ductions, strabismic deviation, MRD1, and MRD2. Bivariate and multivariate statistics were performed. The study included 21 patients. Mean ± SD age was 61.5 ± 12.6 years and 71.4% were female. Reduction in proptosis ≥2 mm was achieved in 71.4% of the sample. Stage and grade were not significant predictors of outcome. Treatment with teprotumumab resulted in a 2.5 ± 1.8 mm reduction of proptosis (P < 0.001), 2.2 ± 1.4 reduction in CAS (P < 0.001), and 16.9 ± 19.3 degree improvement in extraocular motility (P < 0.001). There were no significant differences for change in CAS, proptosis, ductions, or MRD2 between different grades and stages of disease. Total strabismus and MRD1 improvement were greater in the active stage of disease (P < 0.05). Three cases of dysthyroid optic neuropathy, refractory to methylprednisolone therapy improved after initiation of teprotumumab. Treatment of TED with teprotumumab in a heterogeneous patient population is associated with improvement in proptosis, extraocular motility, and CAS. Patients beyond those defined in the clinical trials, including those affected by stable stage, milder grade, and vision-threatening TED may benefit from this therapy. There are, however, limits on the overall efficacy of this medication in the management of certain physical characteristics in TED including eyelid position and strabismus.

A pilot study on the use of prednisolone-encapsulated liposomes for the treatment of moderate-to-severe Graves' orbitopathy with reduced systemic steroid exposure.

To demonstrate that long-circulating PEGylated liposomal prednisolone is a safe and effective therapy in patients with active moderate-to-severe Graves' orbitopathy. Open-label, proof-of-concept, multicentre pilot study. Ten patients with moderate-to-severe Graves's orbitopathy, who were euthyroid for at least three months. Long-circulating PEGylated liposomal prednisolone 150mg was administered intravenously twice, with 2-week interval. Total follow-up was 12months, with visits at baseline, week 2, 6, 13, 26 and 52. Physical, laboratory and ophthalmological examinations were performed. Response to treatment was defined as a reduction in Clinical Activity Score by ≥2 points; palpebral aperture by ≥3mm; soft tissue signs by ≥2 grades; exophthalmos by ≥2mm; and motility by >8 degrees or improvement in diplopia score. A response was sustained when equally observed at weeks 6 and 13. One patient achieved a sustained response according to the predetermined definition. All patients showed a decrease in Clinical Activity Score after one infusion, with a mean decrease of two points. The Clinical Activity Score was ≤1 at week 52 for all patients. Improvement was also observed in the soft tissue signs. Most of the adverse events were mild and of a transient nature. Two patients required further treatment with intravenous methylprednisolone. This pilot study showed a positive effect of long-circulating PEGylated liposomal prednisolone on the Clinical Activity Score in patients with moderate-to-severe Graves's orbitopathy, resulting in fewer hospital visits and possibly less glucocorticoid-related side-effects.

SAT-554 Teprotumumab in Graves' Orbitopathy: Extended Outcome Analyses

Objective A multicenter, double-masked, randomized, placebo-controlled, phase two trial of 88 patients with active, moderate-to-severe Graves’ orbitopathy (GO) has demonstrated a significant and rapid response to teprotumumab, an insulin-like growth factor 1 receptor inhibitory monoclonal antibody, when compared with placebo after 24 weeks (N Engl J Med 2017; 376:1748). We now report extended primary and secondary outcome analyses. Methods Seven weeks after final dose of study medication (week 28), the primary and secondary endpoints were analyzed in teprotumumab intent-to-treat patients as compared with placebo to assess possible relapse. This included the primary composite endpoint of percentage patients with ≥2 points reduction in clinical activity score (CAS, seven-point scale) and a reduction of ≥2 mm in proptosis, secondary endpoints of proptosis, CAS, diplopia grade, specific GO quality of life questionnaire (GO-QoL), and exploratory analyses of clinical severity, all in the study (more severely affected) eye. Results Thirty-one of 42 (74%) teprotumumab- and six of 45 (13%) placebo- treated patients reached the primary outcome at treatment week 28 (p<0.001). Response was maintained from end of treatment period (week 24) in 93% of those teprotumumab-treated patients who responded. Proptosis response was similar to the primary outcome, with 55% of those receiving teprotumumab having a high response (≥3mm decrease). Gender, race, smoking or baseline proptosis values did not impact proptosis response. At week 28, 37/42 (88%) of those receiving teprotumumab and 27/45 (60%) getting placebo reached the CAS outcome (p=0.003). All individual CAS components were different from placebo (p≤0.04) except eyelid erythema (p=0.06). Assessment of CAS and severity of GO favored teprotumumab: chemosis (percent of patients ≥1 grade reduction; p=0.11), swelling of eyelid (percent of patients ≥1 grade reduction; p=0.01) and lid aperture (percent of patients ≥2 mm reduction; p=0.09). From baseline there was a reduction in constant diplopia (36% vs 9.5%) and increase in those with no diplopia (9.5% vs. 50%) in the teprotumumab group. At week 24, significantly more teprotumumab-receiving patients had improved by ≥one grade than placebo (62% vs. 22%, p<0.001). Improvement of diplopia grade remained significant at week 28 off drug. Overall GO-QoL was higher in those receiving teprotumumab than in patients getting placebo (p<0.001). Teprotumumab did not affect thyroid function, which was stable in both study groups through the treatment phase and follow-up. Conclusions Teprotumumab reduced the composite primary outcome of proptosis and CAS, as well as improved diplopia and GO-QoL significantly at seven weeks following study treatment discontinuation. This analysis also indicates that proptosis can serve as a primary and sensitive outcome for future trials of therapeutic response in GO.

Orbital Radiotherapy Plus Concomitant Steroids in Moderate-to-Severe Graves' Ophthalmopathy: Good Results After Long-Term Follow-Up.

BackgroundOrbital radiotherapy (RT) is an effective and consolidate treatment for steroid-refractory Graves’ ophthalmopathy (GO); however, long term effects are not well known.ObjectivesThe aim of this study was to evaluate the long term efficacy and toxicity of orbital RT plus concomitant systemic steroids in a population of patients with moderate-to-severe GO or with eyesight threatening symptoms refractory to steroids.MethodsForty patients with moderate-to-severe GO or with eyesight threatening symptoms not responsive/resistant to steroids were treated with orbital RT at the dose of 20 Gy in 10 fractions plus concomitant steroids. Clinical activity score (CAS) and symptoms status were evaluated to determine response to the treatment.ResultsWe reported overall improvement of symptoms, in particular, a regression at 1-year of diplopia in 32.5% eye movement impairment in 42.5%, eyesight in 27.5% and a 2 point reduction in CAS. After a median time of 56 months 21.9% of the patients underwent orbital decompression for relapse of GO, 4.8% received surgical correction of strabismus, and 2.4% received eyelid lipectomy. Acute toxicity was mild; grade 1 - 2 keratitis occurred in 19.5% of the patients and grade 3 keratitis was observed in 2.4% of the patients. Cataract occurred in 7.4% of the patients after a median time of 24-month-follow-up. No secondary malignancies were reported.ConclusionsOur results reported the long-term efficacy and the good tolerance of orbital RT. The combination of RT plus steroids in this setting may avoid or delay performing the surgery in some cases.

Randomized controlled trial of rituximab in patients with Graves' orbitopathy.

Graves' orbitopathy (GO) is a potentially sight-threatening disease for which available medical therapy is not uniformly successful. Multiple case series suggest that rituximab (RTX) may be effective therapy for GO patients. To determine the efficacy of RTX in GO. It is a prospective, randomized, double-masked, placebo-controlled trial. The study was conducted at a large academic private practice. Twenty five patients with active moderate to severe GO were enrolled, and 21 completed the study to the primary endpoint. Two RTX infusions (1000 mg each) or two saline infusions were given 2 weeks apart. The primary endpoint was a reduction in clinical activity score (CAS) assessed as a continuum and separately as improvement by ≥ 2 points at 24 weeks. Secondary endpoints included success and failure rates, proportions showing clinically significant improvement in proptosis, lid fissure width, diplopia score, lagophthalmos and disease severity, and changes in those parameters, orbital fat/ muscle volume and quality-of-life. The treatment groups were similar in all parameters at baseline. The last observation was carried forward if the patient discontinued prematurely. No differences were found in the proportions of patients showing CAS improvement at 24 weeks (25% placebo; 31% RTX, P = .75) or in CAS decrease from baseline to 24 or 52 weeks [mean 1.5 points (1.8 SD) placebo; 1.2 (2 SD) RTX at 24 weeks, P = .73]. Similarly, there were no differences between groups in any of the secondary endpoints at either 24 or 52 weeks. There were four adverse events (AE) in 3/12 placebo patients and 11 AE in 8/13 RTX-treated patients; 5/6 moderate or severe AE occurred in the RTX group. RTX offered no additional benefit over placebo to our patients with active and moderate to severe GO and carried with it non-negligible adverse effects.

New immunosupressants in the treatment of thyroid-associated ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is an inflammatory eye disease associated with thyroid autoimmune disorder.The traditional treatments have yielded limited efficacy but with some side effects.Recently,researches have shown that some new immunosupressants may be used for the treatment of TAO with significantly improved symptoms,and reduction in clinical activity score. Key words: Thyroid-associated ophthalmopathy; New immunosupressant; Treatment

Low Dose Orbital Radiotherapy for Thyroid Eye Disease

Purpose: The use of low dose orbital radiotherapy for thyroid eye disease (TED) remains controversial. This is a review of patients with TED treated with radiotherapy in our department over the last twelve years.Methods and Materials: Fifty-nine consecutive patients received low dose orbital radiotherapy of 20 Gray (Gy) for active TED at the Beatson Oncology Centre. Their records were retrospectively reviewed and data including duration of symptoms, clinical activity score (CAS) pre- and post-orbital radiotherapy, immunosuppression requirement, subjective assessment and range of rehabilitative surgery was collected.Results: Before orbital radiotherapy, all fifty-nine patients had an initial response to glucocorticoids and therefore presumed to have active phase thyroid eye disease. They received retro-orbital radiotherapy of 20 Gy in 12 fractions over 2 weeks. After treatment, only five patients remained on steroids and only one patient had CAS ≥ 3 at last follow up. Response (change in CAS) to orbital radiotherapy was statistically significant from 3.17 ± 1.75 standard deviation (SD) to 0.73 ± 0.92 SD (P < 0.001) at mean follow up of 6.5 months. There was a reduction in CAS at each subsequent follow up for all subgroups when the patients were grouped according to disease severity i.e. mild TED(CAS 1–2), moderate (CAS 3–4), severe CAS (5–7) and optic neuropathy.Conclusions: We believe orbital radiotherapy has a definite role to play in the treatment of active thyroid eye disease. The majority of our patients experienced a reduction in their clinical activity scores after orbital radiotherapy and this was irrespective of the severity of thyroid eye disease.