Extraocular Muscle Enlargement and Thyroid Eye Disease-like Orbital Inflammation Associated with Immune Checkpoint Inhibitor Therapy in Cancer Patients

Abstract

TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti-cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction.

Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

“…Several case reports have described rare ophthalmic side effects including Graves’ ophthalmopathy or a condition resembling such ( 2 , 50 , 77 , 79 , 80 , 81 ). Signs and symptoms typical of Graves’ and ICI-induced ophthalmopathy include proptosis, eye pain, conjunctival redness, periorbital edema, ophthalmoplegia, and swelling of extraocular muscles on MRI.…”

“…In the latter, however, euthyroidism and negative thyroid-stimulating hormone receptor antibodies (TRAbs) were observed, although increased TPOAbs and TgAbs might be present. Thus, a distinct inflammatory condition called thyroid eye disease (TED)-like orbital inflammatory syndrome ( 80 ) or inflammatory orbitopathy ( 79 ) can be suspected.…”

“…Patients with Graves’ orbitopathy often benefit from high-dose GCS treatment ( 77 ). Similarly, such treatment was helpful in resolving symptoms in most cases with TED ( 80 ), although prolonged treatment may occasionally be needed ( 81 ).…”

“…However, immunotherapy should be withheld in patients with severe hypothyroidism or thyrotoxicosis until their general condition and laboratory results improve with appropriate endocrine therapy. In cases of orbitopathy, immunotherapy should be stopped and carefully reintroduced after individual assessment ( 45 ) but should be discontinued in severe or refractory cases ( 80 , 81 ).…”

Time to dissect the autoimmune etiology of cancer antibody immunotherapy

“…Graves' disease is a rare cause of immunotherapy-related hyperthyroidism generally following the use of ipilimumab. Graves' ophthalmopathy may also occur (59,60). High-dose steroids and antithyroid drugs are used successfully to treat this condition (54,61).…”