Jonathan C P Roos1,2, Rachna Murthy3,4,5. 1. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 2. Department of Ophthalmology, Ipswich Hospital, Ipswich, UK. 3. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. rachna.murthy@addenbrookes.nhs.uk. 4. Department of Ophthalmology, Ipswich Hospital, Ipswich, UK. rachna.murthy@addenbrookes.nhs.uk. 5. Thyroid Eye Disease Service, Department of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. rachna.murthy@addenbrookes.nhs.uk.
Abstract
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.
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.
Authors: Lei Zhang; Fiona Grennan-Jones; Carol Lane; D Aled Rees; Colin M Dayan; Marian Ludgate Journal: J Clin Endocrinol Metab Date: 2011-12-07 Impact factor: 5.958
Authors: G Lanzolla; M N Maglionico; S Comi; F Menconi; P Piaggi; C Posarelli; M Figus; C Marcocci; M Marinò Journal: J Endocrinol Invest Date: 2022-07-13 Impact factor: 5.467