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Intravenous (i.v.) glucocorticosteroids (GCs) constitute the first-line treatment for active and moderate-to-severe Graves' orbitopathy (GO). In cases of persistent disease, rituximab, a monoclonal anti-CD20 antibody, may be used, although studies have yielded conflicting results. In case 1, a 50-year-old female heavy smoker presented with severe bilateral disfiguring eyelid edema of four months, bilateral exophthalmos and a clinical activity score (CAS) of 5/7. Laboratory investigation showed thyrotoxicosis and high thyroid-stimulating immunoglobulin (TSI) levels [32 IU/L (normal &lt;1.75]. After minor improvement by i.v. methylprednisolone and standard retrobulbar radiotherapy (20 Gy), her visual acuity progressively declined to "hand motion". Rituximab was administered (two pulses of 500 mg, two weeks apart), with significant response. At 3 1/2 years of follow-up, CAS is 0/7 and CD20+ lymphocytes remain at the lower normal range. In case 2, a 78-year-old non-smoker male was referred for management of severe active GO, one month after total thyroidectomy for Graves' thyrotoxicosis (TSI: 6.74 IU/L). Over the preceding two-three months, severe GO manifested with chemosis, constant diplopia, loss of color vision and acuity of 1/10 bilaterally (CAS: 7/7). Following partial response to i.v. methylprednisolone and concomitant radiotherapy, rituximab (two pulses of 500 mg each, two weeks apart), was administered. Vision partially recovered and GO remains in remission one year later, even after 131 I (100 mCi) administration for papillary thyroid carcinoma (TSI: 0.9 IU/L and CD20+ count at the lower normal range). In conclusion, rituximab may be an effective second-line therapy in GO patients, providing long-lasting remission.

Enduring remission of active and sight-threatening Graves’ orbitopathy with rituximab: report of two cases