The challenge of second line immunotherapy in Gravesí ophthalmopathy

Alice Irwin1, Aditi Sharma1, Vassiliki Bravis1, Vickie Lee2, Tessa Fayers2, Ahmad Aziz2, Rashmi Akshikar2, Stephen Robinson1, 1St Maryís Hospital,

2Western Eye Hospital, Imperial College Healthcare NHS Trust


The management of Gravesí orbitopathy (GO) aims to tackle visual impairment, inflammation and ultimately long-term fibrosis. For patients with GO in the moderate-to-severe active phase, current evidence advocates intravenous (iv) glucocorticoids +/- orbital radiotherapy and the position of EUGOGO is clear on that. Second line or steroid-sparing immunotherapies have more sparse evidence, with cyclosporine, methotrexate and mycophenolate mofetil (MMF) being used by different units.


Cases: A 40-year old female non-smoker was diagnosed with bilateral GO in 2012, despite rendered euthyroid. She received 12 weeks of IV methylprednisolone and concomitant orbital radiotherapy. Her disease remained stable until 2016, when she developed sight-threatening orbitopathy. This improved with orbital decompression surgery and she reached stable visual acuity and colour vision. However, persistent pain and diplopia dictated escalation to MMF therapy. Multiple infections (chest, urine) and rectal bleeding were adverse effects that led to its discontinuation. Thyroid surgery is being considered.


A 79-year old male ex-smoker presented with sight threatening bilateral GO (right eye 6/36 best corrected (6/30 pinhole), left eye 6/18 best corrected (6/12 pinhole)) and restriction of gaze. He received inpatient IV pulsed methylprednisolone (3 days of 1g/day), followed by urgent orbital decompression surgery. He then completed weekly IV methylprednisolone with concomitant radiotherapy. At that point, his visual acuity remained compromised (right eye NPL best corrected, left eye 6/9 best corrected). MMF therapy was commenced but he discontinued that himself due to gastrointestinal symptoms. He currently has persistent diplopia but a CAS of 0 with stable optic nerve function bilaterally. With overall vision improvement compared to pre-treatment (right eye 6/36 unaided, left eye 6/12 unaided), he is not keen on further therapies.


A 72- year old female non-smoker presented with diplopia and restriction of upward gaze, in the context of a new diagnosis of Gravesí disease in 2017. She was commenced on block and replace therapy and was rendered euthyroid. Weekly IV methylprednisolone was administered (12 weeks) but her CAS remained at 3. She was given oral prednisolone and MMF. She suffered intolerable leg cramps and discontinued the drug. She is now having a further course of IV methylprednisolone and concomitant orbital radiotherapy.

Discussion: Steroid sparing immunotherapy does not have a clear evidence base in GO. MMF is a generally well-tolerated immunosuppressive agent that is now also used in the treatment of GO. For such patients, there can be challenges with such second line, steroid-sparing immunosuppression often with difficult to tolerate side effects. An on-going MDT approach that supports informed patient choice is imperative, despite dilemmas for therapy.