Asymmetric TED is a reasonably common occurrence in the course of TED and has been identified as a significant contributor to psychosocial distress and impaired quality of life [5]. Although TED is typically bilateral and symmetric, TED should be considered in the work up of asymmetric orbital inflammatory disease.

Asymmetric TED has been reported to have a prevalence of 9–41% of patients [1, 2]. Our findings report a prevalence of 33%. The reported prevalence of asymmetric TED varies across studies due to differences in the definition of asymmetry, the clinical stage of disease and inter-observer variations in the clinical assessments. Studies that have evaluated patients later in the course of disease are likely to have a lower prevalence of asymmetric disease, as some patients with asymmetric disease go on to develop symmetric disease [2]. Nevertheless, it is important to keep asymmetric TED in the differential list of patients with asymmetric orbital disease.

The epidemiology of asymmetric TED has been studied previously, with conflicting results. Some studies suggest that asymmetric disease is more prevalent in males, whilst others have failed to show such a difference [1, 6]. Asymmetry has also been associated with older age in a previous study, although most previous studies have not commented on associations with age [6, 7]. Our study did not find a difference in the gender or sex composition of asymmetric TED patients compared to symmetric TED patients.

The pathophysiology of asymmetric TED has not been elucidated, and several potential mechanisms have been proposed including asymmetric distribution of antigen, and anatomical differences causing differential blood flow or lymphatic drainage [3]. One study investigated whether sleeping position may be associated with asymmetric disease and did not find an association [7]. Normal anatomic differences between orbits (such as differences in globe protrusion) may become more pronounced in the setting of active orbital inflammation, manifesting as asymmetric disease. Our study found the found the asymmetric orbit to have significantly higher muscles volumes compared to its contralateral orbit, thus muscle expansion is one of the likely contributing factors to the development of asymmetric proptosis.

Asymmetric disease has been associated with higher clinical activity scores, and more severe disease [6, 8]. Perros et al. [6] reported that asymmetric patients had a mean CAS of 3.0 compared to symmetric patients who had a mean CAS of 1.7. This may be due to the fact that asymmetric disease is more common in the earlier stages of TED [2]. Regardless, the treatment of asymmetric TED does not differ from symmetric TED. Other reported associations of asymmetric disease include euthyroid/hypothyroid status. Eckstein et al. [9] reported a prevalence of 23% of asymmetric disease in euthyroid/hypothyroid patients, defined by a proptosis difference of greater than or equal to 3 mm, compared to 4.8% in hyperthyroid patients. We however did not find a significant correlation between asymmetry and thyroid status, anti-TPO levels or anti-TSH receptor antibody levels, possibly due to type 2 error.

One of the main challenges in determining the clinical and radiological associations of asymmetric disease is the lack of a universal, standardised definition for asymmetric disease. Most studies have used a difference in Hertel measurements of either more than 2 mm or 3 mm to define asymmetric disease [1, 2, 5, 9]. Others have used definitions based on the presence of asymmetric clinical symptoms and signs such as differences in lid swelling or erythema, conjunctival redness or palpebral aperture difference of more than 2 mm [6, 7]. These definitions are based on clinical assessments, which can vary significantly between readers [10]. The lack of a universal definition likely accounts for many of the differences seen in terms of associations of asymmetric TED with age, gender, thyroid status and disease severity. A more objective definition of asymmetric disease, based on more objective markers such as radiologically derived proptosis or muscles volumes may help to standardise the definition of asymmetric TED and allow for comparisons between studies.

Limitations to this study include its retrospective nature. As a result, it was not possible to determine the inter-rater reliability of the Hertel exophthalmometry measurements.

Asymmetric TED is reasonably common and may be seen in one-third of TED patients. The extraocular muscles volumes are higher in the asymmetric orbit compared to its contralateral orbit, suggesting muscle volume expansion to be an underlying contributor to asymmetry. In future, use of more objective parameters to define asymmetric TED is required to enable reliable comparisons between studies.