This study aimed to identify a simple and convenient quantitative MRI parameter that can measure the degree of LGP and predict the activity of TAO. Our findings suggest the following: (1) MRI is a simple, reproducible, and objectively quantifiable method for measuring LGP, which can aid in the diagnosis and staging of patients with TAO; (2) high diagnostic accuracy can be achieved with simple imaging sequences; and (3) LGP evaluation combined with the CAS appears to be useful for distinguishing active and inactive TAO.
Early diagnosis and accurate staging of inflammatory activity in patients with TAO is important in terms of selecting a clinical treatment regimen and may improve the prognosis [8]. The CAS suggested by Mourits et al. [15] is a clinical tool based on redness, swelling, pain, and impaired function and is widely used for assessment of disease activity in TAO. Several studies have indicated that the CAS has high predictive value with respect to the outcome of immunosuppressive treatment [9, 16]. However, the CAS relies on the subjective judgment of clinicians and therefore has relatively poor comparability and cannot be used to quantify pathological changes. Moreover, the CAS does not directly reflect the degree of inflammation and edema in the orbital tissues. Therefore, the clinical diagnosis and treatment of TAO typically require the CAS to be combined with imaging and histological examinations in order to assess inflammatory activity.
Previous studies have used CT and MRI for quantitative assessment of the lacrimal glands to assist clinicians in the diagnosis and staging of TAO [5, 7, 17]. Imaging parameters have confirmed that the volume of the lacrimal gland is greater in patients with TAO than in healthy controls and is associated with inflammatory activity in TAO [5–7, 18]. Furthermore, Bingham et al. [6] found a marked positive correlation between the volume of the lacrimal gland and the CAS. Thus, the importance of lacrimal gland involvement in the diagnosis of TAO has been recognized.
However, calculation of lacrimal gland volume is complicated and too time-consuming for clinicians to perform in everyday clinical practice. In the present study, we found that LGP was significantly greater in patients with active TAO than in those with inactive TAO. Furthermore, there was a significant positive correlation between LGP and the CAS. ROC curve analysis indicated that an LGP value of 13.65 mm could be the optimal threshold for discriminating active and inactive TAO with high sensitivity and specificity. Therefore, LGP is a simple quantitative measurement that could be helpful in improving the diagnostic power of the CAS in the clinical evaluation of patients with TAO.
This study found positive correlations among the degree of LGP, EOM volume, and proptosis. With the development of imaging technology, changes have been observed in the lacrimal glands of patients with TAO. In 1981, Trokel et al. [19] described enlargement and enhancement of the lacrimal glands accompanied by enlarged extraocular muscles on CT images. Similarly, Nugent et al. [20] found that an anteriorly displaced lacrimal gland on CT was associated with clinical palpability and optic neuropathy in 83.3% of patients.
In view of our present findings, we suggest that the mechanism of LGP in patients with TAO involves inflammatory edema of the retrobulbar structures due to increased disease activity, resulting in enlargement and congestion of the orbital tissue. Thus, the lacrimal gland is pushed forward, leading to LGP. Studies of the hormones involved in Graves’ disease [21, 22] have demonstrated that lacrimal acinar cells contain thyroid-stimulating hormone receptors on their surface and that there is a strong correlation between the presence of thyroid antibodies and dysfunction of the lacrimal gland. Furthermore, Gagliardo et al. [11] confirmed a linear correlation between the thyrotropin receptor antibody level and the degree of LGP in patients with TAO. A pathological study also demonstrated that changes in the lacrimal gland were similar to those in the retrobulbar tissue in patients with TAO, namely, multifocal infiltration of lymphocytes and hyperplasia of adipose tissue [23]. As previously mentioned, some studies have suggested that the acinar cells in the lacrimal gland are further targets of TAO, and inflammation is the most likely cause of its enlargement [17, 24]. Therefore, we hypothesize that another reason underlying LGP is that the fibrous periosteal connections between the lacrimal gland and the orbital septum are unable to withstand enlargement of the lacrimal gland in patients with TAO.
We found no significant effect of patient age on the degree of LGP. Therefore, we believe that an impact of advancing age on LGP can be excluded. Despite the age-related increase in laxity of the lacrimal support structures, involvement of the lacrimal gland may be an independent pathogenic feature of TAO.
This study has several limitations. First, the sample size was relatively small. Nevertheless, we believe that the findings provide a basis for further studies on lacrimal gland changes in patients with TAO. Second, the imaging parameters used for the lacrimal gland were not associated with the inflammatory factors in tears and secretory function or pathological changes in the gland. This will be a topic of future research for the purpose of determining the characteristics of the lacrimal gland in the pathogenesis of TAO from an imaging perspective.