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 ?