Figure 1. AAION of the right eye. Diffuse ‘chalk-white’ or pallid optic disc oedema is characteristic of giant cell arteritis.
Dr JY Tong
BSc(Med)Hons BMed MD
Discipline of Clinical Ophthalmology University of Sydney
Dr Clare Fraser
MBBS MMed FRANZCO
Associate Professor of Neuro-ophthalmology and Ophthalmic Education, University of Sydney
Consultant Neuro-Ophthalmologist, Sydney Eye Hospital St Vincent’s Hospital
Save Sight Institute Discipline of Clinical Ophthalmology, University of Sydney
Giant cell arteritis (GCA) is a granulomatous vasculitis that affects medium-sized muscular arteries, particularly the cranial arterial branches of the aortic arch.
Risk factors include age (>/= 50 years), gender (female predominance) and being of Northern European/Caucasian descent. It remains unclear whether previous infections have a role in the pathogenesis of GCA; in particular, Chlamydia pneumoniae, parvovirus B19, herpes virus type 1 and type 2, and varicella zoster virus have been investigated.1
Patients with GCA often present to their optometrist or ophthalmologist with anterior ischaemic optic neuropathy (AION) causing acute severe monocular vision loss, which can rapidly progress to become bilateral. Inflammation of the posterior ciliary arteries can cause a posterior ischaemic optic neuropathy (PION).
In either case, vision loss is often preceded by ischaemic symptoms of ocular pain, diplopia, ptosis, amaurosis fugax or coloured positive transient visual obscurations (TVOs). TVOs suggest transient choroidal ischaemia and hypoperfusion of the optic nerve head. In GCA, the duration varies from minutes to hours, unlike the briefer episodes experienced in papilloedema.
Systemic symptoms including jaw claudication, headache and scalp tenderness are important features to characterise in the clinical history. Jaw claudication refers to masseter muscle pain after a brief period of chewing. Headache is typically new or different, severe and throbbing in quality, and diffuse or localised to the temporal or occipital regions. Patients with scalp tenderness often complain of pain when combing their hair or an aversion to wearing hats.
Concurrent polymyalgia rheumatica in GCA is common, which manifests as morning stiffness and pain of the axial and large joints (neck, shoulders and hips). Prominent constitutional symptoms include malaise, weight loss and fever. Occult GCA occurs in 20 per cent of patients, where associated symptoms are absent.2
Vision loss is often severe, to the magnitude of 6/60 or worse, particularly for GCA associated with arteritic AION (AAION). If vision loss is unilateral, there will be a relative afferent pupillary defect. Eye movements and cranial nerve examination are important. Diplopia can be caused by single or multiple cranial neuropathies, or localised ischaemia of ophthalmic artery branches supplying the extraocular muscles. Diplopia correlates with a positive temporal artery biopsy (TAB) and is associated with incident and subsequent vision loss.3,4
Ocular ischaemic syndrome is a rare complication of GCA that often precedes the development of AION. Relevant signs include hypotony (subclinical ciliary body ischaemia), corneal oedema, uveitis and cotton wool spots. Fundus examination typically demonstrates diffusely ‘chalk-white’ optic disc oedema (Figure 1). Simultaneous occlusion of the central retinal artery and cilioretinal artery is a pathognomonic sign (Figure 2).
Figure 2. AAION with cilioretinal artery occlusion of the right eye. Cilioretinal artery ischaemia is highly suggestive of giant cell arteritis.
External signs of GCA are a thick, tender, non-compressible and non-pulsatile temporal artery, and in advanced cases, scalp necrosis. Scalp tenderness can be elicited by light palpation in the region of the temporal arteries.
There remain no validated diagnostic criteria for GCA. The American College of Rheumatology states that three out of five criteria are required to diagnose GCA: age >/= 50 years, new-onset localised headache, tender or reduced pulsatility of superficial temporal artery, ESR >/= 50 and abnormal biopsy specimen. However, its clinical utility has been refuted in favour of a TAB in all patients to guide management.5 Jaw claudication, neck pain and raised CRP have the highest association with TAB-positive specimens.2 Currently, a new chewing gum test is being developed and validated as a standardised clinical assessment of jaw claudication.6
As soon as the diagnosis is considered, the patient needs to be urgently referred to an ophthalmologist for a same-day consultation. If not available, patients must be directed to an emergency department for admission under neurology or rheumatology, with input from ophthalmology. High-dose steroid therapy should not be deferred for the TAB and should be commenced immediately, as it improves visual outcomes and prevents vision loss.7
GCA should not be a diagnostic consideration in anyone younger than 50 years of age. Rheumatological conditions associated with non-GCA arteritic AION that can mimic GCA include:
• polyarteritis nodosa
• ANCA-associated vasculitides (granulomatosis with polyangiitis, Churg-Strauss syndrome)
• systemic lupus erythematosus
• rheumatoid arthritis.
On blood tests, inflammatory markers CRP and ESR are often elevated, with a combined sensitivity of 97 per cent. However, there can be non-concordance, which is typically a high CRP and normal ESR.8 Patients on systemic immunosuppressants can have normal inflammatory markers, so negative blood tests do not exclude GCA.
TAB is the gold-standard diagnostic test for GCA. It can be performed up to 10 days from starting steroid treatment. A specimen of at least 2 cm in length should be taken, with fine serial sections of 0.5 mm examined. Histopathology of an abnormal biopsy will demonstrate intimal thickening containing regions of granulomatous inflammation and endovascular occlusion (Figure 3). A contralateral biopsy can be performed if the ipsilateral side is negative, but only up to five per cent of such specimens are positive.9
Figure 3A. Haematoxylin and eosin-stained slide of a TAB specimen demonstrating intimal thickening and narrowed arterial lumen. Reproduced with permission (Kuo et al6)
Figure 3B. Higher magnification demonstrates an inflammatory infiltrate of lymphocytes and macrophages. Reproduced with permission (Kuo et al6)
Standard automated perimetry is useful in documenting visual field defects in GCA, particularly in the contralateral eye. AION scotomas tend to occur in an altitudinal or arcuate pattern respecting the horizontal meridian, while central scotomas predominate in arteritic PION.10
Optical coherence tomography can be used to provide a baseline for the affected eye or show early oedema in the contralateral optic disc. Fluorescein angiography is a useful adjunct for demonstrating delayed or patchy choroidal filling, and delayed central retinal arterial filling.
GCA is a sight- and life-threatening ophthalmic emergency and must be treated promptly. Delaying treatment can lead to disease progression to the fellow eye and irreversible vision loss in one-third of patients within one day, one-third in one week and one-third in one month.11 Involvement of the carotid circulation can cause transient ischaemic attacks or strokes.
High-dose steroid therapy is often required for 18-24 months. There is no accepted weaning regimen, though most clinicians will reduce the dose based on symptoms and inflammatory markers (ESR and CRP).
The aim of promptly treating GCA is to protect the fellow eye and prevent visual deterioration. In untreated GCA, the risk of AAION in the fellow eye is 25-50 per cent. With appropriate treatment, the risk of recurrent AAION in the fellow eye drops to < 10 per cent.12
The same eye often has a very poor prognosis for recovery and up to 30 per cent may even deteriorate after steroids have been initiated. Only four to five per cent of patients demonstrate mild improvement in visual acuity and visual fields.12 Earlier commencement of steroid therapy may improve prognosis. Ongoing review and collaboration with ophthalmologists and physicians is necessary throughout the treatment period and thereafter.
A 65-year-old woman presented with horizontal double vision, which was worse at distance. She complained of scalp pain while combing her hair and had stopped wearing her golf cap. Her diet had consisted exclusively of soups for the previous week.
She reported occasionally waking with generalised stiffness and ache causing difficulty getting dressed but attributed this to ageing. Her medical history included varicella during infancy, hypertension and type 2 diabetes mellitus. Her ocular history was significant only for bilateral cataract surgery.
Best corrected visual acuity was 6/60 OD and 6/9 OS. Pupil examination revealed a subtle right RAPD. On cover test, the right eye had a subtle esotropia in primary gaze. On ocular motility testing, there was limited abduction of the right eye, suggesting a right abducens nerve palsy. IOP was 14 mmHg OD and 16 mmHg OS. Dilated fundus examination revealed diffusely pallid right optic disc oedema. Her right superficial temporal artery was tender, thickened and non-pulsatile on palpation (Figure 4).
Figure 4. In giant cell arteritis, the superficial temporal artery is prominent due to being thickened and dilated. On palpation, it is often tender, non-compressible and non-pulsatile.
She was admitted to hospital for intravenous steroids, and a temporal artery biopsy confirmed giant cell arteritis
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