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Debate Immunosuppressive therapy vs Radiotherapy in the management of Graves’ Ophthalmopathy

Debate Immunosuppressive therapy vs Radiotherapy in the management of Graves’ Ophthalmopathy. Kaushik Pandit. In Favour of Radiotherapy. MD, MNAMS, DM (Endo) Consultant Endocrinologist Fortis Hospital, Belle Vue Clinic, Kolkata & Research Scientist Dept. of Endocrinology,

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Debate Immunosuppressive therapy vs Radiotherapy in the management of Graves’ Ophthalmopathy

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  1. DebateImmunosuppressive therapy vs Radiotherapyin the management of Graves’ Ophthalmopathy Kaushik Pandit In Favour of Radiotherapy MD, MNAMS, DM (Endo) Consultant Endocrinologist Fortis Hospital, Belle Vue Clinic, Kolkata & Research Scientist Dept. of Endocrinology, IPGME&R, Kolkata

  2. Background (Pathophysiology) • Orbital fibroblasts in the endomysium & perimysium of extraocular muscles- are the primary target • Retroorbitalpreadepocyte fibroblast-like cell- are the primary target • T-cell mediated

  3. Options • Immunosuppresion • Glucocorticoids • Cyclosporine, Cyclophosphamide, Azathioprine, Plasmapheresis • External Beam Radiotherapy

  4. Radiation • Mechanism • Clonogenic death • Apoptotic death • Radiation induced death of Inflammatory cells, lymphocytes • Reduction in muscle swelling • Local Effect (restricted to the orbit only)

  5. Results (Retrospective Trials) • Stanford- 311 pts 1968-1988- • 80% had soft tissue responses, • 58% complete response Peterson IA et al. Int J RadiatOncolBiol Phys 1990; 19:259–264. • France- 199 pts 1977-1996- • 26% complete response vs 48% partial response Beckendorf V et al. Int J RadiatOncolBiol Phys 1999; 43:805–815.

  6. Results (Prospective Trials) • 56 pts- (vs Prednisone)- Response rate similar (~50%)- Side effects more in Prednisone & Radiotherapy better tolerated Prummel MF, et al. Lancet 1993; 342:949–954. • 60 pts (vs placebo- sham radiation)- 60% vs 31% response rate. Motility improved 82% vs 20%. Mourits MP, et al. Lancet 2000; 355:1505–1509.

  7. Immunosuppression • Generalised Effect !! • Relapse after withdrawal !! • Side effects !!

  8. Side Effects (glucocorticoids) • Immunosuppression • Increased appetite • Irregular heartbeat • Loss of libido • Menstrual irregularities • Mood disturbance • Oral rash • Osteoporosis • Paresthesias • Poor wound healing • Proximal myopathy • Skin rash • Stomach ulcers • Weakness • Weight gain • Acne • Adrenal insufficiency • Arthralgia • Avascular necrosis of the hip • Cataracts • Cushingoid features • Diabetes • Depression • Easy bruisability • Fluid retention • Glaucoma • Headache • Hirsutism • Hypertension

  9. RadiotherapyWhy underutilised ? • Availability- only in tertiary care centres • Expertise- scarce

  10. Radiation- Side Effects • Cataracts (dosimetric errors/ high dose) • Retinopathy (DM increased risk) • Radiation induced tumor (1.2%) Kinyoun JL, et al. Arch Ophthalmol 1984; 102:1473–1476. Snijders-Keilholz A, et al. RadiotherOncol 1996; 38:69–71.

  11. Any tangible reason to discard Radiotherapy as First Choice ?

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