Retinal artery occlusion

Summary

Retinal artery occlusion is an ophthalmic emergency requiring immediate assessment and transfer to a stroke centre. Ischaemia to the retina often causes severe visual loss, which may be irreversible if retinal circulation is not rapidly re-established. The majority of cases are caused by atherosclerosis-related thrombosis and embolism.

Aetiology

Any vessels supplying the eye may become occluded. The central retinal artery is the first branch of the main artery supplying the eye: the ophthalmic artery. After entering the eye, the central retinal artery branches into superior and inferior vessels that supply nerve fibres in the inner retina as well as the optic nerve.

Another branch of the ophthalmic artery is the posterior ciliary arteries, which give rise to the cilio-retinal artery. The ciliary arteries supply the outer retina.

Blood flow through any of these vessels may become obstructed, producing a retinal artery occlusion. The causes of retinal artery occlusion are:

• Embolism - embolism and thrombus are the main causes. Emboli most commonly originate from atherosclerotic plaques in the carotid artery; the ophthalmic artery is the first branch of the internal carotid artery, so emboli can easily travel into the eye. Emboli can also travel to the eye from the heart, in conditions such as arrhythmia (e.g. atrial fibrillation), mitral valve prolapse and bacterial endocarditis.

• Thrombus - 1/3 of young patients have a thrombophilic disorder (e.g. antiphospholipid syndrome, hyperhomocystinaemia)

• Inflammatory vessel wall damage (e.g. giant cell arteritis (GCA), systemic lupus erythematous, granulomatosis with polyangiitis, polyarteritis nodosa)

• Traumatic vessel wall damage

• Vasospasm (e.g. migraine)

• Systemic hypotension

Risk factors

The risk factors for retinal artery occlusion are similar to those for ischaemic stroke:

• Age

• Male gender

• Smoking

• Hypertension

• Hyperlipidaemia

• Cardiovascular disease (CVD)

• Diabetes

• Obesity

• Coagulopathy

We shall now discuss the various types of retinal arterial occlusive disease, before exploring systemic assessment and management.

Central retinal artery occlusion (CRAO)

Central retinal artery occlusion occurs when there is a blockage in the central retinal artery.

Symptoms

• Sudden, profound loss of vision

• Painless (except in GCA)

Signs

• Severely reduced visual acuity. In GCA and ophthalmic artery occlusion, light perception may be absent. Note that cilioretinal arteries, which arise from the posterior ciliary artery system, are present in 〜45% of people (and 〜30% of eyes). These arteries provide an alternative blood supply to the retina; central vision may be preserved in patients who have a cilioretinal artery supplying a critical macula area.

• Profound Relative Afferent Pupillary Defect (RAPD)

Fundoscopy

Note that the fundus may appear normal early in the course of CRAO.

• ‘Cherry-red spot’ appearance: ischaemia causes the nerve fibre layer of the retina to become oedematous, and so it opacifies, producing a pale retina. The fovea is a thin area with no overlying nerve fibre layer, hence the orange reflex from the intact choroid at this point stands out, producing a ‘cherry-red spot’ appearance. Retinal oedema can take hours to develop. Note that in patients with a cilioretinal artery, part of the macula will remain normal colour.

• The peripapillary area (the area surrounding the optic disc) may be especially oedematous and opacified

• Small haemorrhages may be found

• Emboli are visible in 20% of cases

• Over days-weeks, the ‘cherry-red spot’ appearance disappears, and optic atrophy, patchy inner retinal atrophy and vessel sheathing set in

• 〜2% of eyes develop retinal/disc neovascularisation

A classic image of CRAO with a cherry-red spot, retinal oedema and narrowing of the vessels. Image courtesy of Fieß et al.

Other ophthalmic investigations:

• Ocular coherence tomography (OCT): may show a highly reflective embolic plaque

• Fluorescein angiography (FA): shows a delay in arterial filing and sluggish blood flow in the retinal arteries

• Electroretinography (ERG): may be useful in subtle cases. A diminished b-wave is present due to retinal ischaemia. ERG may be normal in cases where blood flow has returned to normal (despite poor visual acuity)

Branch retinal artery occlusion (BRAO)

As the name implies, in branch retinal artery occlusion, one of the branches of the central retinal artery is occluded.

Symptoms

• Sudden painless altitudinal or sectoral loss of vision. Altitudinal visual loss means loss of vision in the upper or lower horizontal half of the visual field; sectoral visual loss means loss of a section of the normal visual field. Particularly if central vision is spared, BRAO may go unnoticed.

Signs

• Variable visual acuity - loss of central vision carries a worse prognosis. The defect rarely recovers.

• RAPD

Fundoscopy

Fundus signs may be subtle.

• Attenuation of arteries and veins, with segmentation of the blood column

• White oedematous retina corresponding to the region of ischaemia

• Emboli may be seen, especially at bifurcation points

Other ophthalmic investigations

• Visual field testing: confirms the defect

• FA: delay in arterial filling; hypofluorescence of the affected segment (due to retinal oedema blocking the background fluorescence)

Fundoscopy showing BRAO. Note the area of retinal ischaemia and the arrow pointing to a cholesterol embolus (”Hollenhorst plaque”). Image courtesy of Jones and Peall.

Cilioretinal artery occlusion

As mentioned above, cilioretinal arteries (found in 〜30% of people) provide a second blood supply to the central macula. Thus, if cilioretinal arteries supplying the fovea are present in a patient with CRAO, central vision may be preserved. Rarely, the cilioretinal artery can become occluded. Cilioretinal artery occlusion can be:

• Isolated - rare, may occur in young patients with a vasculitis

• Combined with central retinal vein occlusion (CRVO) - not uncommon, occlusion is transient. Carries a better prognosis than the isolated type

• Combined with anterior ischaemic optic neuropathy - typically affects patients with GCA, carries a poor prognosis

Isolated cilioretinal artery occlusion. Note the retinal oedema adjacent to the fovea. Image courtesy of Aktaş et al.

Amaurosis fugax

Amaurosis fugax is a cause of transient visual loss in one or both eyes. The name is derived from the Greek “amaurosis”, meaning dark, and the Latin “fugax”, meaning fleeting.

Causes are classified as:

• Embolic: the most common cause of amaurosis fugax is a carotid artery embolism, and in clinical practice amaurosis fugax is largely considered to be embolic in origin.

• Haemodynamic

• Ocular (e.g. papilloedema, intermittent angle-closure glaucoma)

• Neurologic (e.g. retinal migraine)

• Idiopathic

Symptoms

• Transient, painless loss of vision - described as a ‘dark curtain descending’ on the eye, usually lasting a few minutes

• Usually monocular (termed ‘transient monocular visual loss’, TMVL), but can be binocular (’transient binocular visual loss’, TBVL)

Patients can have many attacks, varying in frequency, from several times a day to once every few months. Attacks may be accompanied by an ipsilateral cerebral TIA. Just like with retinal arterial occlusion, there is a high risk of stroke in amaurosis fugax, so immediate assessment and management is required.

Systemic assessment of retinal arterial occlusive disease

Retinal arterial occlusion is a type of ischaemic stroke, thus following diagnosis by an ophthalmologist, urgent referral to a stroke centre is vital. The stroke team will enquire about the following:

• Smoking history and other modifiable risk factors (discussed above)

• Symptoms of GCA (e.g. headache, jaw claudication, scalp tenderness, weight loss, limb girdle pain)

The following tests should be carried out:

• Heart rate (to detect arrhythmia e.g. atrial fibrillation)

• Blood pressure (to detect hypertension)

• Cardiac examination (to detect a murmur)

• ECG (to rule out arrhythmia or other cardiac disease)

• Platelets (on the FBC), ESR, CRP: these are all raised in GCA

• HbA1c, lipids

• Carotid duplex ultrasound (to look for carotid artery stenosis)

In select patients, the following tests may be considered:

• Hypercoagulability workup to investigate for antiphospholipid syndrome, autoimmune conditions, hypercoagulable states and other inflammatory disorders: in patients <50 years old

• Echocardiography: to investigate for structural cardiac disease

• 24-hour ECG: to investigate for intermittent arrhythmia

• Cranial MRI/CT: to rule out intracranial/orbital pathology

• Other blood tests e.g. plasma protein electrophoresis (for myeloma), thyroid function tests (especially if AF is present), blood cultures, syphilis serology

Management of retinal arterial occlusive disease

Acute management

Patients with retinal artery occlusion may simultaneously have a silent ischaemic stroke, so rapid transfer to a stroke centre is vital.

If retinal circulation is not re-established before retinal infarction develops, vision loss is irreversible. In humans, there is thought to be a window of 〜6 hours before damage is irreversible.

Unfortunately, however, treatment is rarely effective. The following may be tried if the patient presents within 24 hours, although there is a lack of evidence for clear benefit, and each treatment carries risks.

• Ocular massage using a three-mirror contact lens (aiming to mechanically collapse the arterial flow, improving circulation and potentially dislodging an embolus)

• Topical apraclonidine and timolol, and IV acetazolamide (to lower intraocular pressure)

• ‘Rebreathing’ into a paper bag (elevating blood carbon dioxide levels may promote vasodilation)

• Breathing a high oxygen (95%) and carbon dioxide (5%) mixture - ‘carbogen’

• Transluminal Nd:YAG laser embolysis/embolectomy: evidence is reporting good final visual results, but vitreous/subretinal haemorrhage occurs as a complication in 〜50% of cases

• Thrombolysis

Systemic management

The risk of stroke is increased for the first few days after retinal artery occlusion or amaurosis fugax. Furthermore, vision may not be restored in the affected eye, so it is vital to protect the second eye. Systemic management involves:

• Risk factor modification e.g. quitting smoking

• Antiplatelet therapy (provided there are no contraindications)

Some patients may require:

• Oral anticoagulation (e.g. warfarin): important in patients with AF

• Carotid endarterectomy: in patients with symptomatic carotid stenosis >70%

Reviewing patients

In CRAO, the patient should be reviewed by an ophthalmologist at 3-4 weeks, 2 months, and 3 months as a minimum, to detect neovascularisation. Neovascularisation is a complication that can cause pain or further visual loss in the affected eye. If detected, panretinal photocoagulation should be performed, and intravitreal injection of VEGF inhibitor may be considered.

In BRAO, the patient should be reviewed at 3 months.

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020.

2. Taarnhøj, Nina C. B. B., et al. ‘Heritability of Cilioretinal Arteries: A Twin Study’. Investigative Opthalmology & Visual Science, vol. 46, no. 10, Oct. 2005, p. 3850. DOI.org (Crossref), https://doi.org/10.1167/iovs.05-0177.

3. Fieß, Achim, et al. ‘Anterior Chamber Paracentesis after Central Retinal Artery Occlusion: A Tenable Therapy?’ BMC Ophthalmology, vol. 14, no. 1, Dec. 2014, p. 28. DOI.org (Crossref), https://doi.org/10.1186/1471-2415-14-28.

4. Jones, Robin G., and Adrian Peall. ‘Sudden Unilateral Visual Field Loss’. Journal of Emergencies, Trauma and Shock, vol. 2, no. 3, 2009, pp. 211–12. PubMed Central, https://doi.org/10.4103/0974-2700.55352.

5. Aktaş, Serdar, et al. ‘Idiopathic Isolated Cilioretinal Artery Occlusion Treated with Hyperbaric Oxygen Therapy’. Turkish Journal of Ophthalmology, vol. 46, no. 5, Oct. 2016, pp. 244–47. PubMed Central, https://doi.org/10.4274/tjo.87513.