Statistics from Altmetric.com
Chronic ocular pain may have many causes and can be a frustrating problem for both patient and doctor alike. We describe two patients who had similar symptoms and eye findings who had been unable to relieve their pain with conventional analgesia. We postulate a cause for their pain and describe our experience of a treatment strategy using a standard dose of botulinum toxin injection into an extraocular muscles.
A 56 year old white woman presented with what was initially thought to be a right orbital cellulitis but investigations and clinical course subsequently suggested a non-infectious idiopathic inflammatory aetiology. Her history suggested orbital myositis and she described right sided facial weakness, nausea, and right sided ptosis. She had a 9 month course of oral steroids and despite this needed tramadol, paracetamol, and flurbiprofen to control her pain. Her symptoms and examination findings slowly stabilised until she was left with marked limitation of upgaze in her right eye. Her symptoms did not change over the next 3 years, at which point she was referred to our care. When she attempted to look up she described a juddering sensation and severe pain just above the eye. She rarely had pain at night but was still using regular oral ibuprofen for pain relief. Her pain was exacerbated by reading or looking at the computer and she complained of vertical diplopia.
On examination she had limitation of abduction and elevation of her right eye and prisms did not improve her symptoms. A tentative diagnosis of inflammatory spasm was made. She was treated with botulinum toxin injection to her right inferior rectus. Two weeks later there was much less tightness and discomfort in the orbit but she had diplopia in all positions of gaze and was forced to occlude one eye. Three months later the pain was much improved but she still found the diplopia intolerable and declined further treatment.
A 46 year old white man presented complaining of chronic constant ocular discomfort which followed strabismus surgery 8 years earlier for an A-pattern exotropia with diplopia on downgaze. The pain was worsened by prolonged television watching and prisms in his glasses did not help. Pain was much worse on upgaze and right gaze, which were limited. Oral non-steroidal anti-inflammatory agents (NSAIDs) did reduce the pain a little but only when taken in high doses (100 mg three times daily flurbiprofen).
On examination he had a right hyperphoria, with an A-pattern esotropia and an abnormal head posture for distance. He still had diplopia. Botulinum toxin was injected into his left medial rectus muscle, which resulted in a profound reduction in his symptoms, leaving him with a small exophoria. His diplopia resolved completely after 10 weeks. The “pressure sensation” and pain in the right eye recurred after about 6 months, this time with no diplopia. He had a further injection of toxin 8 months after the first which again significantly improved his pain but gave him diplopia for 3 weeks. He continues to take flurbiprofen 50 mg three times daily orally.
The pain demonstrated by these two patients is typically much worse in certain directions of gaze and particularly during prolonged gaze holding such as when reading or watching television. It had a clear precipitating event and the most remarkable feature is that it had persisted for over 2 years in each case without significant progression or regression. No active disease process could be found to account for the continued pain. The pain is severe and responds only to high doses of analgesics, particularly NSAIDs. None of our patients felt that their pain was satisfactorily controlled by their analgesics.
We believe that there may be a process of chronic low grade inflammation affecting the extraocular muscles or the tissues around them which is exacerbated by continued contraction and relaxation of the same muscles. Muscular spasm perhaps triggered by this inflammatory process may be the cause of the most severe pain and this could account for the exacerbations of pain in certain directions of gaze and on prolonged gaze holding activities. Ocular muscle ischaemia, perhaps caused by constricting scar tissue, remains a possibility but the onset of the pain is very fast making this less likely.
The pain relief seen in our patients may simply be the result of paralysing an inflamed muscle but there is growing evidence for a separate antinociceptive effect of botulinum toxin.1 No direct peripheral cutaneous antinociceptive effect could be shown by Blersch et al2; however inhibition of release of substance P has been demonstrated in vitro and it can be hypothesised that botulinum toxin treatment may reduce the local release of nociceptive neuropeptides from either cholinergic neurons or from C or A delta fibres in vivo.3 The mechanisms by which botulinum toxin may relieve pain, including a possible analgesic effect of botulinum toxin metabolites, are reviewed by Guyer.4
There is a growing literature on the use of botulinum for painful conditions,5 particularly those in which muscle spasm plays a part. These include writer’s cramp,6 postoperative pain in spastic cerebral palsy,7 and perhaps more surprisingly migraine8 and painful tic convulsif.9 Many of the reported uses are single case studies and not all controlled trials have shown a positive effect of treatment.10
It is not possible to rule out a powerful placebo effect in our patients but, whatever the mechanism of action, their pain was vastly improved and botulinum toxin treatment is very safe in competent hands.
In the cases described botulinum toxin served a dual purpose in that it had the potential to improve their ocular deviation for which it is well known and it also reduced the severe ocular discomfort. Unfortunately, the resulting diplopia limited its usefulness in one case but we feel that this treatment should be considered in this unusual group of patients who present a difficult management problem even to the most experienced ophthalmologists.