Rajendram, R; (2014) The Management & Medical Treatment of Thyroid Eye Disease. Doctoral thesis , UCL (University College London).

Abstract

Thyroid eye disease (TED) is a disfiguring autoimmune orbital inflammatory condition that may result in loss of vision and intractable diplopia. Optimal treatment is highly debated as current evidence is conflicting, and long-term outcomes of management within the UK is lacking as a result of small cohorts and variability in individual physician:s treatment plans. I performed a retrospective casenote review of 425 patients presenting to Moorfields Eye Hospital under one consultant between 1997 and 2002 inclusively. Approximately two-thirds of patients (69%) with initial and final exophthalmometer readings (n=257) had a reduction in proptosis of 2mm or more and 67% of the 206 with diplopia at presentation improved by their final visit. Smokers at presentation required strabismus surgery more often than non-smokers (hazard ratio 1.8; p = 0.02, 95% confidence interval 1.08 – 3.22). These results indicate that there is room for improvement in outcomes and that smoking cessation should be emphasised. Orbital radiotherapy is the most controversial of current therapies used worldwide. I performed a systematic review which suggested that radiotherapy is superior to sham radiotherapy (natural history) with a relative risk of 1.92. To provide further Level 1 evidence, I established a multicentre factorial-designed 3 year follow-up randomised controlled trial (RCT) addressing the use of steroids in combination with either radiotherapy, a steroid sparing agent (azathioprine) or both (www.cirted.org). A high screening failure rate early on led to review of entry criteria and appropriate modifications of the protocol increased the proportion of eligible patients progressing to randomisation. At the time of writing recruitment is complete with 512 patients assessed for eligibility, 298 screened, 167 recruited and given a 2 week steroid trial leading to 127 responding and being randomised. The high conversion from recruitment to randomisation (76%) suggested the clinical enrolment criteria were effective for detecting active disease. To identify a novel objective measure of disease activity a nested magnetic resonance imaging (MRI) study was performed to explore the use of diffusion-weighted imaging. This technique was found to be subject to significant artefact and difficult to interpret, and therefore not of benefit in clinical practice. Taken together, the studies in this thesis show that, despite treatment deemed best management, proptosis or diplopia persists in one third of patients and additional medical treatments in the active stage are required to improve outcomes; robust RCTs are needed to provide evidence. Such RCTs are complex and our trial provides a template on which other collaborative work could be based, and therefore encourage homogeneity of outcome measures to allow future meta-analyses.

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