Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED): a multicentre, 2 × 2 factorial, double-blind, randomised controlled trial.

BACKGROUND: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. METHODS: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100-200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for <50 kg, 150 mg 50-79 kg, 200 mg for ≥80 kg). The primary outcomes were a binary composite clinical outcome score and an ophthalmopathy index at 48 weeks, and a clinical activity score at 12 weeks. The primary analysis was based on the intention-to-treat allocation and safety was assessed in all participants. This study is registered with ISRCTN, number 22471573. FINDINGS: Between Feb 15, 2006, and Oct 3, 2013, 126 patients were recruited and randomly assigned to groups: 31 patients to radiotherapy plus azathioprine, 31 to sham radiotherapy and azathioprine, 32 to radiotherapy and placebo, and 32 to sham radiotherapy and placebo. Outcome data were available for 103 patients (54 for sham radiotherapy vs 49 for radiotherapy and 53 for placebo vs 50 for azathioprine), of whom 84 completed their allocated treatment of radiotherapy or sham radiotherapy and 57 continued to take azathioprine or placebo up to 48 weeks. There was no interaction betweeen azathioprine and radiotherapy (pinteraction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98-6·66, p=0·054) for azathioprine and 0·89 (0·36-2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66-28·1, p=0·008) for azathioprine and 1·32 (0·30-4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. INTERPRETATION: In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. FUNDING: National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Giant cell arteritis--presenting as stroke, transient ischaemic attack and dementia.

BACKGROUND: Stroke and multi-infarct dementia are most commonly caused by atherosclerotic disease and are irreversible. Stroke and dementia associated with giant cell arteritis are rare but important to recognise as they may be reversible if diagnosed and treated promptly. OBJECTIVE: This article describes the case of a patient who presented with a cilioretinal artery occlusion, diagnosed as being due to giant cell arteritis. DISCUSSION: In retrospect, it seems likely that a stroke suffered 3 years earlier and mental state deterioration over that period may have been associated with the giant cell arteritis. Therefore, features useful in identifying stroke, transient ischaemic attack and dementia caused by giant cell arteritis are described.

A survey of ocular sports trauma and the role of eye protection.

PURPOSE: The incidence of sports associated ocular injuries presenting to emergency departments is rising. Despite this, eye protection is not widely used in the general population. This survey was conducted to determine the spectrum of ocular sports injuries that presented to the emergency department of an ophthalmic hospital, which serves a large sector of inner city London. The role of eye protection in preventing ocular sports injuries was also investigated. METHODS: All patients who attended the emergency department with sports associated ocular injuries between May and July 2008 were identified. Medical records of these patients were examined. RESULTS: There were a total of 16999 ophthalmic emergency attendances. 48 (0.28%) patients presented with sports related ocular injuries. The outcomes of the consultations were: 13 (27.1%) patients discharged from the emergency department, 17 (35.4%) had reviews arranged in the emergency department, 18 (37.5%) referred to subspecialties. The mean presenting LogMAR visual acuities of patients that were discharged, reviewed in the emergency department, and referred to subspecialties were 0.01 (±0.33), 0.48 (±0.75), and 0.31 (±0.61) respectively. Visual acuities were better by 0.39 (95% CI 0.01-0.77, p=0.042) in patients who were discharged compared to patients who were reviewed in the emergency department or referred to subspecialties. Evaluation of records revealed that no patients wore eye protection and none were given advice regarding prevention of future injuries. CONCLUSION: Results from this survey show that ocular sports injuries account for a proportion of ophthalmic emergency attendances with a potential impact on service provision. It is essential that ophthalmologists, optometrists and other healthcare professionals are aware of the potential ocular morbidity from sports trauma and the importance of providing advice on the prevention of such injuries.

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED) trial: a multi-centre, double-masked, factorial randomised controlled trial.

BACKGROUND: Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed.The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED) trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. METHODS/DESIGN: Patients with active thyroid eye disease will be randomised to receive (i) azathioprine or oral placebo and (ii) radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure) at 12 months and secondary end-points include quality of life scores and health economic measures. DISCUSSION: The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a) robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b) constructing effective inclusion and exclusion criteria to select for active disease; and (c) selecting pragmatic outcome measures. TRIAL REGISTRATION: Current controlled trials ISRCTN22471573.

Giant cell arteritis presenting with scalp necrosis--the timing of temporal artery biopsy?

Scalp necrosis in patients presenting with clinical features suggestive of giant cell arteritis is rare. The immediate concern is that temporal artery biopsy might further compromise scalp circulation. We report a case of extensive scalp necrosis caused by giant cell arteritis. Temporal artery biopsy performed after 14 days was not associated with any significant damage and still provided florid evidence of the disease. Rapid and complete scalp healing was achieved with aggressive treatment.

Fatigable ptosis and pseudoretraction caused by myasthenia gravis.

The case is presented of a 59-year-old woman with myasthenia gravis. Fatigable ptosis and pseudoretraction caused by the myasthenia gravis are illustrated in a series of clinical photographs.