Quantitative analysis of the clinical activity of thyroid-associated ophthalmopathy

Abstract

Purpose : Thyroid-associated ophthalmopathy (TAO) is the most common cause of unilateral or bilateral proptosis in an adult. As an autoimmune inflammatory disorder, active TAO is evaluated by Clinical Activity Score (CAS) and managed optimally by immunosuppression. In this study, we aimed to evaluate activity of TAO with octreotide scintigraphy and the level of serum extraocular muscle antibodies.

Methods : This retrospective study comprised 108 adult patients with active TAO (CAS≥3), 73 with inactive TAO (CAS<3), 128 with Graves’ disease (GD) without ophthalmopathy and 100 healthy subjects. Moderate-to-severe active TAO patients (CAS≥5) received intravenous injection of methylprednisolone 500 mg/w × 6w followed by 250 mg/w × 6w, for a cumulative dose of 4.5 g; the response rate was 85%. The eyes suffering from mild active patients (3≤CAS≤4) received periocular injection of triamcinolone acetonide 20 mg/3w × 5 times; the response rate was 90%. ⁹⁹Tc^m-octreotide scintigraphy and serum levels of calsequestrin antibodies were detected before and after treatment.

Results : ⁹⁹Tc^m-octreotide scintigraphy was positive in active TAO patients (97%). The uptake ratio (UR) was elevated (P<0.05), and showed a significant correlation with CAS (r=0.816, P<0.01). After treatment, both UR and CAS decreased significantly (P<0.05). The Receiving-Operator-Characteristic Curve (ROC) showed that the best UR threshold for discriminating active and inactive TAO was 1.34 (sensitivity, 100%; specificity, 89.4%). The level of serum calsequestrin antibody was higher in active TAO (P<0.05), showed a significant correlation with CAS (r=0.738, P<0.05), and also decreased after treatment (P<0.05). The best serum calsequestrin antibody threshold of the ROC curve was 138 ng/L (sensitivity, 88.4%; specificity, 89.2%). Moreover, six GD patients (4.69%) with elevated calsequestrin developed active TAO 12 weeks later.

Conclusions : ⁹⁹Tc^m-octreotide scintigraphy played a critical role in the evaluation of the clinical activity and therapeutic efficacy of TAO. Autoimmunity against calsequestrin in the pathogenesis of the eye muscle components may provide further objective evidence of myopathy in active TAO. Furthermore, calsequestrin antibody may predict myopathy active TAO.

This is a 2020 ARVO Annual Meeting abstract.