Abstract
Background: Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED) is a severe ocular manifestation of Graves’ Disease. It manifests as an autoantibody mediated reaction to the thyroid hormone stimulating receptor (TSH-R), these receptors are closely linked with the insulin-like growth factor-1 receptors (IGF-1R). The TSH-R antibodies play a major role in the pathogenesis of TED. The activation of the TSH-R and IGF-1R on orbital fibroblasts and adipocytes lead to IGF-1 expression. This initiates inflammation, fibroblast proliferation and accumulation of glycosaminoglycans in the orbital tissue. Treatment modalities include glucocorticoids, orbital radiation and orbital decompressions. Recent understanding of the molecular basis of TED has resulted in targeted therapy with Teprotumumab, an inhibitory monoclonal antibody against IGF-1R. There is limited literature on the outcomes of Teprotumumab use after orbital decompression surgery.
Clinical Case: 43-year-old female presented with symptoms of diplopia, periorbital pain, dry eyes and tremor. Ocular exam: Vision was correctable to 20/20 in each eye, restricted motility, bilateral lid edema, lid retraction with superior scleral show and conjunctival injection. Clinical Activity Score > 4. Diagnostic tests: TSH 0.00 undetectable (N:0.5-5.0mIU/L) FT4 3.19 (N:0.7-1.9ng/dL) TSI thyroid stimulating immunoglobulin 490% of baseline (N: 130% of baseline). Diagnosis of Graves’ disease with associated orbitopathy was made. In addition to medical management for Graves’ thyroid disease she was referred to ophthalmology. She was treated with high dose steroids for 4 weeks with no resolution of symptoms. She was then referred to an oculoplastic surgeon for bilateral orbital decompressions which resulted in mild improvement in diplopia but a residual proptosis. The decision was made to treat with teprotumumab, which had recently been FDA approved. Patient reported improved symptoms without complicating enophthalmos. Review confirmed improved proptosis on Hertel Exophthalmometry. The right eye improved from 22 mm to 16 mm and the left eye from 21 mm to 17 mm (N <20.1 mm Caucasian females) with preserved visual acuity, improved lid retraction, resolved conjunctival chemosis and decreased periorbital pain after 6 doses of Teprotumumab therapy.
Conclusion: Graves’ orbitopathy can result in debilitating symptoms affecting quality of life. Targeted molecular therapy such as teprotumumab is an effective treatment even after orbital decompression.
Reference: Ting, M., Ezra, D.G. Teprotumumab: a disease modifying treatment for graves’ orbitopathy. Thyroid Res13, 12 (2020). https://doi.org/10.1186/s13044-020-00086-7
The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy
