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Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves' orbitopathy.
Eye 2019 April
BACKGROUND: Rapamycin (alternatively known as sirolimus) is a macrolide immunosuppressant commonly used for organ transplantation. It acts both on lymphocytes through the mechanistic target of rapamycin (mTOR) pathway to reduce their sensitivity to interleukin-2 (IL-2) and, importantly, also has anti-fibrotic properties by acting on myofibroblasts. The latter have been implicated in the pathogenesis of thyroid eye disease (TED).
AIM: To describe successful treatment and reversal of extraocular muscle fibrosis in TED with sirolimus.
METHODS: Case report and literature review with clinic-pathological correlation.
RESULTS: A patient with Graves' orbitopathy (GO) developed significant ocular motility restriction, which was unresponsive to steroids and conventional immunosuppression. Unlike these prior treatments, rapamycin therapy improved the diplopia and fields of binocular single vision over a period of months. There were no adverse effects directly attributable to the treatment.
CONCLUSION: With its low renal toxicity and ability to specifically target the underlying fibrotic pathways in GO, rapamycin may prove a useful adjunct to standard immunosuppressive regimes. We encourage further reporting of case series or the instigation of controlled trial.
AIM: To describe successful treatment and reversal of extraocular muscle fibrosis in TED with sirolimus.
METHODS: Case report and literature review with clinic-pathological correlation.
RESULTS: A patient with Graves' orbitopathy (GO) developed significant ocular motility restriction, which was unresponsive to steroids and conventional immunosuppression. Unlike these prior treatments, rapamycin therapy improved the diplopia and fields of binocular single vision over a period of months. There were no adverse effects directly attributable to the treatment.
CONCLUSION: With its low renal toxicity and ability to specifically target the underlying fibrotic pathways in GO, rapamycin may prove a useful adjunct to standard immunosuppressive regimes. We encourage further reporting of case series or the instigation of controlled trial.
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