The diagnosis of CRAO is usually straightforward. The cause of a CRAO is, however, broad and varies with the age and sex of the patient and the existence of known medical conditions. Giant cell arteritis in persons aged 50 years or older is especially critical to diagnose and a high Westergren ESR suggests the diagnosis.

The differential diagnosis of acute persistent monocular visual loss includes a number of other ophthalmic emergencies: ischaemic optic neuropathy (AION and PION), acute occlusion of the central retinal vein, detachment of the macula, acute closed angle glaucoma, sudden vitreous or macular haemorrhage, as well as factitious visual loss.

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