Post on 11-Jan-2016
description
Debate
Immunosuppressive therapy vs Radiotherapy in the management of Graves’
Ophthalmopathy
Kaushik Pandit
MD, MNAMS, DM (Endo)Consultant EndocrinologistFortis Hospital, Belle Vue Clinic, Kolkata
& Research ScientistDept. of Endocrinology,IPGME&R, Kolkata
In Favour of Radiotherapy
Background (Pathophysiology)
Orbital fibroblasts in the endomysium &
perimysium of extraocular muscles- are the
primary target
Retroorbital preadepocyte fibroblast-like cell- are
the primary target
T-cell mediated
Options
Immunosuppresion› Glucocorticoids› Cyclosporine, Cyclophosphamide,
Azathioprine, Plasmapheresis
External Beam Radiotherapy
Radiation
Mechanism
› Clonogenic death
› Apoptotic death
Radiation induced death of
Inflammatory cells, lymphocytes
Reduction in muscle swelling
Local Effect (restricted to the orbit only)
Results (Retrospective Trials)
Stanford- 311 pts 1968-1988- › 80% had soft tissue responses, › 58% complete response
Peterson IA et al. Int J Radiat Oncol Biol Phys 1990; 19:259–264.
France- 199 pts 1977-1996- › 26% complete response vs 48% partial
response Beckendorf V et al. Int J Radiat Oncol Biol Phys
1999; 43:805–815.
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.
Immunosuppression
Generalised Effect !!
Relapse after withdrawal !!
Side effects !!
Side Effects (glucocorticoids)
Acne Adrenal insufficiency Arthralgia Avascular necrosis of the hip Cataracts Cushingoid features Diabetes Depression Easy bruisability Fluid retention Glaucoma Headache Hirsutism Hypertension
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
RadiotherapyWhy underutilised ?
Availability- only in tertiary care
centres
Expertise- scarce
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. Radiother Oncol 1996; 38:69–71.
Any tangible reason to discard Radiotherapy as
First Choice ?