Central Retinal Artery Occlusion

Embolic Causes (~40–50%)

Embolism is the most common identifiable cause of non-arteritic CRAO. Emboli reaching the central retinal artery most commonly lodge at or just proximal to the lamina cribrosa, where the vessel is smallest in calibre. Embolic sources in CRAO are identical to those in BRAO:

• Cholesterol emboli (Hollenhorst plaques): From atheromatous plaques at the ipsilateral carotid bifurcation or aortic arch; glistening, refractile, yellow-orange crystals; most common embolic type; urgent carotid Doppler mandatory
• Fibrin-platelet emboli: From cardiac mural thrombus (AF, MI, dilated cardiomyopathy), prosthetic valves, or carotid plaque surface; white, elongated, may fragment; higher stroke risk than cholesterol emboli; associated with AF in particular
• Calcific emboli: From calcified aortic or mitral valves; solid white, opaque; lodge at or proximal to the disc; associated with severe valvular disease; rarely move spontaneously
• Tumour emboli: Cardiac myxoma fragments, non-bacterial thrombotic endocarditis (marantic endocarditis) in malignancy; important in younger patients with underlying cancer or cardiac tumour

Thrombosis In Situ (~40–50%)

• Atherosclerotic thrombosis at the lamina cribrosa: The CRA passes through a fibrous tunnel at the level of the lamina cribrosa, where atherosclerotic narrowing and plaque rupture can precipitate in-situ thrombosis; the most common non-embolic mechanism in older patients with multiple cardiovascular risk factors
• Hypertensive arteriolopathy: Medial hypertrophy and intimal fibrosis from chronic hypertension dramatically narrow the CRA lumen at the lamina cribrosa, predisposing to in-situ thrombosis independent of embolic events
• Vasospasm: In younger patients without conventional risk factors; associated with migraine with aura, Raynaud phenomenon, cocaine, sympathomimetic drugs, and ergotamine; may present as amaurosis fugax before permanent CRAO

Arteritic Cause — Giant Cell Arteritis (GCA)

• Mechanism in GCA: Granulomatous vasculitis with giant cell infiltration of the media and adventitia of medium and large vessels causes transmural inflammation, intimal hyperplasia, and occlusive thrombosis of the posterior ciliary arteries (most commonly) and central retinal artery
• Clinical clues for GCA: Age >60 (rarely below 50); new headache (typically temporal); scalp tenderness; jaw claudication (pathognomonic); temporal artery tenderness or nodularity; polymyalgia rheumatica symptoms (proximal limb girdle aching, morning stiffness); weight loss; fever; anaemia; elevated ESR (>50 mm/h) and CRP
• Ophthalmic artery involvement in GCA: GCA may also occlude the ophthalmic artery — a more proximal occlusion that eliminates choroidal as well as retinal perfusion; this abolishes the cherry red spot (both retina and choroid are white) and causes even worse visual prognosis; critical to distinguish from CRAO on FA and clinical grounds

Other Causes

• Coagulopathy / thrombophilia: Antiphospholipid syndrome, protein C/S deficiency, Factor V Leiden, hyperhomocysteinaemia — particularly relevant in younger patients (<50) without cardiovascular risk factors
• Elevated intraocular pressure: Acute angle-closure glaucoma crisis — IOP elevation sufficient to exceed diastolic perfusion pressure occludes the CRA; also observed following retrobulbar injections and orbital compartment syndrome
• Orbital compartment syndrome: Retrobulbar haemorrhage (from trauma, retrobulbar injection, post-orbital surgery) rapidly elevates orbital pressure, compressing the optic nerve and CRA; requires emergency lateral canthotomy and cantholysis — an orbital emergency
• Inflammatory vasculitis (non-GCA): SLE, Behçet disease, polyarteritis nodosa, sarcoidosis — cause periarterial inflammation and occlusion; important in younger patients with systemic autoimmune disease
• Sickle cell disease: Sickling within the CRA at the lamina cribrosa; particularly at times of systemic stress or hypoxia
• Recreational drugs: Cocaine causes intense vasospasm and promotes in-situ thrombosis in young adults; IV drug use with talc emboli; amphetamines and sympathomimetics
• Perioperative: Prolonged prone positioning (spine surgery), carotid endarterectomy, cardiac bypass, face-down positioning — all may precipitate CRAO through positional compression, arterial hypotension, or embolic shower

Step 1 — Complete Cessation of Inner Retinal Perfusion

Obstruction of the CRA — at or proximal to the lamina cribrosa — simultaneously eliminates arterial inflow to all four retinal quadrants. Unlike CRAO from venous occlusion where venous outflow is blocked, arterial occlusion prevents oxygen and glucose delivery entirely. The inner retina (ganglion cell layer, inner plexiform layer, inner nuclear layer, nerve fibre layer) — which derives its nutrition exclusively from the retinal circulation — becomes globally ischaemic within seconds. The outer retina (outer nuclear layer, photoreceptors, retinal pigment epithelium) is maintained by diffusion from the choroidal circulation and is not immediately affected.

Step 2 — Cytotoxic Oedema and Inner Retinal Whitening

Within minutes of complete arterial occlusion, failure of Na⁺/K⁺-ATPase from ATP depletion causes cytotoxic oedema — intracellular swelling of ischaemic neurones and astrocytes from failure of ionic pump mechanisms. Disruption of axoplasmic transport in the nerve fibre layer leads to focal accumulation of axoplasmic material. These changes render the inner retina opaque and milky-white in appearance — clinically observed as diffuse retinal whitening covering all four quadrants. The whitening is most dense in the perifoveal area and along the nerve fibre layer arcades.

Step 3 — The Cherry Red Spot

The pathognomonic cherry red spot is explained by the unique anatomy of the fovea. The foveola contains no inner retinal layers — it is composed exclusively of cone photoreceptor outer and inner segments, which lie in direct contact with the RPE and are nourished by the intact choroidal circulation. The thin, transparent foveal tissue allows the orange-red choroidal colour (visible through the RPE and Bruch's membrane) to shine through as a bright red spot, contrasting sharply with the surrounding white oedematous inner retina. This is the cherry red spot — present in CRAO because the choroidal circulation to the fovea is preserved, and absent in ophthalmic artery occlusion where the choroid is also ischaemic.

Step 4 — Ischaemic Time Window and Irreversibility

Primate experimental studies (Hayreh, 1990) established that irreversible retinal neuronal damage begins after approximately 90–100 minutes of complete CRA occlusion. After 4 hours, ischaemic damage is severe and largely irreversible. Beyond this window, reperfusion may restore anatomical patency but does not recover lost ganglion cells or nerve fibres. This time-sensitive window is analogous to the therapeutic window in cerebral ischaemia — explaining why experimental treatments targeting the first few hours have been studied, and why prompt presentation and assessment are critical even though no proven ocular treatment currently exists.

Step 5 — Optic Atrophy and Chronic Inner Retinal Loss

Over weeks to months, the acute retinal whitening resolves as oedema fluid reabsorbs. Permanent loss of inner retinal neurons — ganglion cells, inner nuclear layer cells, and their axons within the optic nerve — follows. The optic disc develops progressive pallor from retrograde axonal degeneration, typically detectable clinically 4–6 weeks after the acute event. On OCT, permanent inner retinal thinning is evident as dramatic reduction in the ganglion cell layer and inner plexiform layer thickness across all sectors. The arterioles become sheathed from periarteriolar fibrous tissue. Final visual acuity reflects the degree of foveal ganglion cell and inner nuclear layer loss, as well as any sparing from a cilioretinal artery.

Primary Classification — Arteritic vs Non-Arteritic

The most critical clinical distinction in CRAO is between the arteritic form (caused by giant cell arteritis) and the non-arteritic form (caused by emboli, atherosclerosis, or other non-inflammatory mechanisms). This distinction drives immediate management decisions and prognosis.

CRAO with Cilioretinal Artery Sparing

A cilioretinal artery — present as a normal anatomical variant in approximately 20–35% of eyes — arises from the posterior ciliary circulation rather than the CRA, entering the retina at the optic disc margin. When a cilioretinal artery is present and perfused in the setting of CRAO, it maintains blood supply to the papillomacular bundle and central macular area, producing a sector of spared retina between the disc and fovea.

• Fundus appearance: The characteristic orange-red island of spared retina between the disc and fovea, surrounded by diffuse white ischaemic retina — the "reverse cherry red spot" pattern; the cilioretinal artery remains patent and normally filled
• Clinical significance: Central visual acuity may be 6/12 or better despite complete CRAO of all other retinal sectors; the patient retains reading vision; a critical favourable prognostic modifier
• Important caveat: Cilioretinal artery occlusion in the setting of CRVO (a distinct entity) causes the opposite pattern — central macular ischaemia with peripheral venous congestion

Transient CRAO (Amaurosis Fugax)

Transient complete monocular visual loss — amaurosis fugax — from transient CRA occlusion that spontaneously resolves before permanent ischaemic damage occurs. Patients describe a sudden complete blackout of one eye lasting seconds to minutes, followed by spontaneous recovery of full vision. Fundus is typically normal if the patient is examined after recovery. Represents a retinal TIA — the same emergency management pathway as permanent CRAO and hemispheric TIA applies.

Cardiovascular and Embolic Risk Factors (Major)

• Carotid artery atherosclerosis: Significant ipsilateral carotid stenosis is identified in 40–60% of CRAO patients on vascular imaging; the single most important actionable embolic source; urgent carotid Doppler and neurovascular assessment are mandatory at presentation
• Atrial fibrillation: Cardioembolic source; fibrin-platelet emboli from the left atrial appendage; present in approximately 15–20% of CRAO patients; anticoagulation (DOAC or warfarin) substantially reduces recurrence risk; may require Holter monitoring to detect paroxysmal AF
• Systemic hypertension: Present in 60–75% of CRAO patients; accelerates carotid atherosclerosis; hypertensive arteriolopathy narrows the CRA lumen; the most prevalent co-morbidity in CRAO
• Valvular heart disease: Calcific aortic stenosis, mitral valve prolapse, infective endocarditis; echocardiography is essential to identify cardiac embolic sources
• Prior myocardial infarction / left ventricular thrombus: Mural thrombus at site of infarcted myocardium; dilated cardiomyopathy with reduced ejection fraction
• Hyperlipidaemia: Atherogenic dyslipidaemia drives carotid and aortic atherosclerosis; dyslipidaemia is present in approximately 40–50% of CRAO patients
• Diabetes mellitus: Endothelial dysfunction and atherosclerosis acceleration; also promotes in-situ arteriolar thrombosis
• Smoking: Promotes atherosclerosis, increases platelet aggregation, and reduces fibrinolysis; a major modifiable risk factor
• Patent foramen ovale (PFO): Paradoxical embolism; particularly important in young patients with cryptogenic CRAO; contrast bubble echocardiography (bubble test) is the diagnostic standard
• Aortic arch atherosclerosis: Complex plaques (>4 mm) are an important proximal embolic source; detected on transoesophageal echocardiography

Arteritic Risk — Giant Cell Arteritis

• Age >60: GCA is essentially confined to patients over 50; prevalence increases with age
• Female sex: GCA has a 3:1 female predominance
• Northern European descent: Higher prevalence in Scandinavian and Northern European populations; less common in Asian populations but not absent
• Polymyalgia rheumatica (PMR): Up to 40% of GCA patients have concurrent PMR; PMR itself does not cause ocular complications but its presence increases the probability of GCA

Haematological and Thrombophilic Factors

• Thrombophilia: Antiphospholipid syndrome, Factor V Leiden, prothrombin G20210A, protein C/S deficiency, antithrombin III deficiency, hyperhomocysteinaemia — screen in patients <50 without conventional vascular risk factors or with recurrent events
• Hyperviscosity: Polycythaemia vera, essential thrombocythaemia, multiple myeloma — elevated whole-blood viscosity promotes in-situ thrombosis within the CRA
• Sickle cell disease: Sickling within the CRA, particularly at times of systemic hypoxia or dehydration
• Oral contraceptive pill / HRT: Oestrogen-mediated coagulation activation; particularly relevant in young women with cryptogenic CRAO

Ocular and Iatrogenic Risk Factors

• Elevated intraocular pressure: Acute angle closure crisis — extreme IOP elevation reduces the arteriovenous perfusion pressure below the diastolic CRA pressure, causing functional arterial occlusion
• Retrobulbar injection: Inadvertent intra-arterial injection or haematoma formation causing orbital compartment syndrome and CRA compression
• Perioperative positioning: Prolonged prone positioning during spine surgery, inadvertent globe compression from anaesthetic mask — mechanical occlusion of orbital vessels
• Orbital cellulitis / orbital tumour: Extrinsic compression of orbital structures raising orbital pressure and compromising CRA perfusion

Pathognomonic Acute Funduscopic Signs

• Diffuse inner retinal whitening — all four quadrants: The global inner retinal oedema produces a pale, chalky-white or milky appearance covering all four retinal quadrants; the whitening is most intense in the perifoveal area where the nerve fibre layer and ganglion cell layer are thickest; the pallor may extend to the extreme retinal periphery; this distinguishes CRAO from BRAO (which whitens only one sector)
• Cherry red spot at the fovea: The single most important and diagnostically specific sign of acute CRAO; the fovea appears as a bright orange-red or cherry-red dot against the surrounding pale white ischaemic retina; produced by choroidal circulation shining through the thin, non-oedematous foveal tissue (no inner retinal layers at the foveola); present from within minutes of occlusion; fades over days to weeks as the surrounding oedema resolves; absent in ophthalmic artery occlusion (choroid also ischaemic)
• Markedly attenuated arterioles: All four major branch arterioles appear pale, thread-like, or virtually invisible; the arterial columns are strikingly thin compared to the companion veins; in complete occlusion, arterioles may appear as ghost vessels without visible blood column
• Box-carring / cattle-trucking: Segmentation of the blood or plasma column within arterioles — alternating segments of blood and clear plasma visible within the vessel lumen; a sign of very low or absent flow; may be seen in all arterioles simultaneously in CRAO; resolves as collateral flow or recanalization develops

Other Acute Signs

• Optic disc pallor / oedema: The disc may appear pale from the outset (hyperacute ischaemia of the optic nerve head) or may develop disc oedema if the posterior ciliary arteries are also compromised (GCA); true disc oedema in non-arteritic CRAO is mild; frank disc oedema should raise suspicion for GCA or ophthalmic artery occlusion
• Relative afferent pupillary defect (RAPD): Almost universally present in acute CRAO; the degree of RAPD reflects the extent of ganglion cell loss; a dense, sluggish RAPD suggests severe ischaemia; absence of RAPD in a patient claiming complete visual loss should raise doubt about the diagnosis or suggest non-organic visual loss
• Visible embolus: Present in approximately 20% of acute CRAO cases; typically at or near the optic disc (at the CRA entry point); type of embolus may be characterised as in BRAO; its absence does not exclude embolic aetiology as emboli may have moved or lysed
• Cilioretinal artery sparing: In patients with a patent cilioretinal artery, an orange-red island of spared retina is visible between the disc and fovea, surrounded by diffuse white ischaemic retina; the cilioretinal arteriole is brighter red and normal-calibre in contrast to the ghost branch arterioles

Chronic / Resolved Phase Signs (Weeks to Months)

• Optic disc pallor: The most prominent chronic finding; diffuse disc pallor from retrograde axonal degeneration of ganglion cell axons in the optic nerve; typically develops 4–6 weeks after the acute event and is complete by 2–3 months; may be sectoral if cilioretinal artery sparing partially preserved function
• Inner retinal thinning on OCT: Marked, global thinning of the ganglion cell layer, inner plexiform layer, and retinal nerve fibre layer across all sectors; the pattern of inner retinal atrophy matches the extent of ischaemia; the outer nuclear layer (ONL) and IS/OS line remain relatively preserved in non-arteritic CRAO where choroidal supply is intact
• Arteriolar sheathing: Periarteriolar white fibrous sheathing in previously occluded vessels; a marker of resolved arterial occlusion
• Optociliary shunt vessels: Rare; may develop at the disc as collateral channels
• Neovascularisation (NVD, NVE, rubeosis iridis): Occurs in approximately 10–20% of CRAO eyes, typically 6 weeks to 3 months after the event; iris rubeosis and angle neovascularisation (with risk of neovascular glaucoma) are important late complications; requires anti-VEGF and PRP

Signs Specific to Arteritic CRAO (GCA)

• Chalky white disc oedema: Intense disc swelling with a characteristic chalky-white appearance — distinct from the pink/grey disc oedema of non-arteritic causes; caused by posterior ciliary artery occlusion affecting the anterior optic nerve blood supply
• Absent cherry red spot (ophthalmic artery occlusion): If GCA occludes the ophthalmic artery proximally, the choroidal circulation is also eliminated; the fovea then has no red choroidal colour to show through — the entire fundus is uniformly white, without the typical cherry red spot
• Temporal artery abnormalities: On examination, the temporal arteries may be tender, nodular, thickened, or pulseless; these are important clinical signs of GCA — the superficial temporal artery should be palpated in all CRAO patients over 50

Presenting Visual Symptoms

• Sudden, profound, complete monocular visual loss: The hallmark of CRAO; onset is almost instantaneous — patients describe sudden complete darkness or blackout of one eye, occurring within seconds; the loss is typically total or near-total (hand motion, counting fingers, or perception of light only); the profound severity distinguishes CRAO from BRAO (where central acuity is usually preserved) and from most other acute visual conditions
• Painlessness: The visual loss of non-arteritic CRAO is entirely painless in the vast majority of cases; this distinguishes it from acute angle closure glaucoma (which causes intense ocular pain), optic neuritis (which causes pain on eye movement), and GCA-associated CRAO where headache and scalp pain are prominent features
• Instantaneous onset: Patients can typically identify the exact moment of visual loss; they describe it as a sudden event while performing a specific activity — reading, watching television, or upon waking; this abruptness distinguishes CRAO from slowly progressive conditions and is consistent with sudden vascular occlusion
• Monocularity: Patients often do not initially realise the loss is monocular; covering one eye reveals the complete loss; bilateral simultaneous CRAO is essentially pathognomonic of a proximal embolic source or GCA; apparent bilateral simultaneous loss is a stroke or chiasmal event until proven otherwise
• Preceding amaurosis fugax: A minority of patients (approximately 10–20%) report prior episodes of transient monocular visual loss that resolved spontaneously — the classic curtain coming down and back up, or a greyout; these episodes represent retinal TIAs preceding the permanent event; a history of amaurosis fugax in the days to weeks before presentation is an important and sometimes missed red flag

Symptoms in Arteritic CRAO (GCA)

• Headache: Typically new-onset, temporal, throbbing; often described as the "worst headache of their life" or qualitatively different from prior headaches; may precede visual loss by days to weeks; not always present — 10–15% of GCA patients have no headache ("occult GCA")
• Jaw claudication: Pain and fatigue of the masticatory muscles when chewing — pathognomonic of GCA when present (specificity >90%); caused by ischaemia of the masseter and temporalis muscles from temporal artery vasculitis; patients often describe stopping mid-meal to rest their jaw
• Scalp tenderness: Tenderness on brushing hair or resting the head on a pillow; caused by inflammation of scalp arteries; patients may describe a tender lump or cord on the side of the head
• Neck pain and stiffness: Vertebral artery involvement in GCA may cause posterior neck pain and occipital headache
• Polymyalgia rheumatica symptoms: Proximal limb-girdle aching and morning stiffness (>45 minutes) affecting the shoulders, upper arms, hips, and thighs; frequently coexisting with GCA; may precede ophthalmic involvement by months
• Constitutional symptoms: Weight loss, fatigue, low-grade fever, malaise, night sweats, anaemia — symptoms of a systemic inflammatory disease
• Transient visual obscuration before CRAO: Amaurosis fugax episodes are particularly common in GCA immediately preceding the permanent event — the so-called "warning episodes"; critical to recognise and treat before permanent loss occurs

Permanent Visual Loss

• Profound permanent visual loss — the primary complication: In the majority of CRAO eyes, final visual acuity is counting fingers, hand motion, or perception of light only; this reflects the irreversible loss of ganglion cells and inner retinal neurons after more than 90–100 minutes of complete ischaemia; approximately 25–30% of non-arteritic CRAO eyes recover VA ≥6/60 — the remainder have permanent severe visual disability
• Permanent monocular visual field loss: Even in eyes recovering some central acuity (through cilioretinal sparing), extensive peripheral field loss from inner retinal atrophy persists; patients may fail driving visual field requirements in the affected eye
• Legal blindness: A significant proportion of CRAO eyes meet the definition of legal blindness (VA <6/60 or visual field <20° in the better eye); patients require low vision rehabilitation and registration

Optic Atrophy

• Diffuse optic disc pallor: Develops 4–8 weeks after acute CRAO; reflects retrograde degeneration of all ganglion cell axons; permanent; associated with permanent severe visual field loss; may affect the nerve fibre layer globally

Neovascular Complications

• Iris neovascularisation (rubeosis iridis): Occurs in approximately 10–20% of CRAO eyes, typically within 3 months; less common than after ischaemic CRVO because in CRAO only the inner retina is ischaemic (outer retina and choroid remain viable via the intact choroidal circulation), producing a lower VEGF load than in CRVO
• Neovascular glaucoma (NVG): Follows angle neovascularisation and synechial angle closure; treated urgently with anti-VEGF injection and pan-retinal photocoagulation; less common than after ischaemic CRVO but remains an important cause of ocular pain and irreversible additional visual loss
• Retinal neovascularisation (NVE/NVD): Seen in ischaemic CRAO eyes with extensive non-perfusion; managed with scatter PRP to the ischaemic retina

Bilateral Blindness (GCA)

Systemic Complications — Stroke and Cardiovascular Events

• Ischaemic stroke: The most feared systemic complication; 90-day stroke risk following CRAO is 8–12%; the same embolic source producing CRAO can simultaneously generate cerebral emboli; concurrent MRI may reveal acute cerebral ischaemia in 15–25% of CRAO patients
• Myocardial infarction: Shared atherosclerotic burden; 5-year MI risk is substantially elevated above age-matched controls
• Recurrent CRAO or BRAO: Risk of further ipsilateral or contralateral retinal arterial events if embolic source is not identified and treated
• Cardiovascular mortality: Long-term cardiovascular mortality is elevated; CRAO is a marker of advanced systemic vascular disease

Carotid Artery Disease

• Ipsilateral internal carotid artery stenosis: Present in 40–60% of CRAO patients; the most important actionable finding; significant symptomatic carotid stenosis (>70%) warrants urgent carotid endarterectomy (CEA) within 2 weeks (NASCET trial); CAS is an alternative in high surgical risk patients
• Contralateral carotid disease: Bilateral carotid atherosclerosis is common; both carotid arteries should be imaged
• Aortic arch plaques: Detected on transoesophageal echo; >4 mm plaques carry high embolic risk; managed with antiplatelet therapy and statin

Cardiac Disease

• Atrial fibrillation: Identified in 15–20% of CRAO patients; may be paroxysmal — requires Holter monitoring (24–48 hours) or implantable loop recorder if AF not detected on initial ECG; anticoagulation with DOACs dramatically reduces stroke and retinal occlusion recurrence
• Structural cardiac disease: Left ventricular thrombus, valvular disease (aortic stenosis, mitral prolapse), cardiomyopathy, intracardiac tumour (myxoma) — echocardiography is mandatory in all CRAO patients
• Patent foramen ovale: Paradoxical venous-to-arterial embolism; contrast bubble echocardiography; PFO closure may be considered in young patients with cryptogenic CRAO

Concurrent Cerebral Ischaemia

• Concurrent acute ischaemic stroke: DWI-MRI studies demonstrate concurrent acute cerebral ischaemic lesions in 15–25% of CRAO patients at the time of presentation; these lesions may be clinically silent but carry risk of progression to symptomatic stroke; urgent MRI brain is indicated in all CRAO patients
• Cerebral microemboli: Transcranial Doppler may detect ongoing microembolic signals from carotid or cardiac sources — informing urgency of vascular intervention
• Cerebral small vessel disease: White matter lesions and lacunar infarcts are more prevalent in CRAO patients than in age-matched controls, reflecting shared small vessel arteriosclerotic disease

Giant Cell Arteritis — Systemic Implications

• Large vessel GCA: In addition to ophthalmic involvement, GCA affects the aorta and its major branches; aortic aneurysm (particularly thoracic aorta) is a long-term complication in approximately 20% of GCA patients; annual aortic imaging is recommended for the first 5 years after GCA diagnosis
• Cerebrovascular disease in GCA: GCA can affect the vertebral and internal carotid arteries, causing posterior circulation strokes and other cerebrovascular events
• Steroid-related systemic complications: Long-term high-dose prednisolone therapy causes osteoporosis, hypertension, hyperglycaemia, Cushingoid features, and infection risk; bone protection (bisphosphonates, calcium/vitamin D) and adjuvant tocilizumab (IL-6 receptor antagonist) reduce cumulative steroid dose

Clinical Diagnosis

CRAO is a clinical diagnosis based on the triad of sudden profound painless monocular visual loss, diffuse inner retinal whitening across all four quadrants, and the pathognomonic cherry red spot at the fovea. The diagnosis is typically made on clinical examination alone within minutes of assessment. Multimodal imaging is essential for confirmation, staging, guiding treatment, and monitoring for complications.

• Visual acuity: Baseline BCVA is critical; may range from 6/12 (with cilioretinal sparing) to perception of light only; VA at presentation is the strongest predictor of final outcome; VA worse than counting fingers at presentation carries a particularly poor prognosis
• Pupil examination — RAPD: A dense RAPD is almost universally present in CRAO; the swinging flashlight test should be performed immediately as part of the acute assessment; absence of RAPD in claimed profound monocular visual loss raises doubt about organic diagnosis
• Intraocular pressure: Must be measured; elevated IOP suggests acute angle closure as a contributing cause; assess the fellow eye for angle closure risk
• Anterior segment slit-lamp examination: Iris examination for early rubeosis iridis (may develop within weeks of acute CRAO); corneal clarity (exclude acute angle closure); assess lens and anterior vitreous
• Colour fundus photography: Essential for baseline documentation; captures the cherry red spot, retinal whitening extent, arteriolar attenuation, visible embolus, disc appearance, and cilioretinal artery status; enables serial comparison as oedema resolves
• Visual field testing: Confrontation fields at bedside; formal Humphrey perimetry (24-2 or 30-2) after the acute phase for driving fitness assessment and documentation

Optical Coherence Tomography (OCT)

• Acute phase: Marked inner retinal hyperreflectivity and swelling affecting the ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and nerve fibre layer (NFL) globally across all sectors; the outer nuclear layer (ONL), IS/OS line, and RPE are typically preserved (maintained by intact choroidal circulation); this "inner retinal infarction" pattern is characteristic of CRA occlusion and distinguishes it from outer retinal pathology
• Chronic phase: Severe global inner retinal thinning — marked reduction in GCL and IPL thickness across all retinal sectors; the degree of inner retinal thinning on OCT correlates with the extent of irreversible neuronal loss and final visual acuity; the outer retina typically appears well-preserved unless there is concurrent choroidal ischaemia (GCA)
• RNFL analysis: Diffuse severe RNFL thinning on circumpapillary OCT corresponding to global ganglion cell axon loss; useful for documentation and prognostication
• Macular GCL mapping: Global GCL-IPL thinning on the macular OCT map; spared macular zone in cilioretinal artery sparing cases creates a characteristic pattern of preserved central GCL surrounded by globally thinned GCL
• Choroidal thickness: In GCA-related CRAO, concurrent choroidal ischaemia may produce choroidal thinning — an important differentiating feature from non-arteritic CRAO

Fluorescein Angiography (FA)

• Absent or severely delayed arterial filling: The most dramatic FA finding; no fluorescent dye reaches the retinal arteries during the normal arterial phase; in complete acute occlusion, the retinal arteries may remain dark throughout the entire angiogram
• Choroidal flushing: The choriocapillaris fills normally and rapidly in non-arteritic CRAO (intact posterior ciliary circulation), confirming that the occlusion is at the CRA level; choroidal filling is absent or delayed in GCA (where posterior ciliary arteries are also affected) or in ophthalmic artery occlusion
• Prolonged arteriovenous transit time: AV transit time (normally 11–12 seconds) is dramatically prolonged in CRAO — may exceed 1–2 minutes in severe cases; venous filling is delayed and incomplete
• Box-carring on FA: The segmentation of blood column visible clinically is confirmed as alternating fluorescent and dark segments within the arteriolar lumina on angiography
• Cilioretinal artery patency: FA demonstrates normal rapid filling of the cilioretinal artery in CRAO with cilioretinal sparing — highlighting the orange-red island of spared retina as an angiographic perfusion island
• Late optic disc staining: Disc hyperfluorescence from staining of ischaemic nerve head tissue on late phase; may be more pronounced in GCA with concurrent anterior optic nerve ischaemia

OCT Angiography (OCTA)

• Dramatic global absence of flow in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) across all four retinal sectors; the entire retinal capillary network appears as a "flow void" — the most comprehensive capillary non-perfusion pattern seen in any retinal vascular disease
• The choriocapillaris flow slab remains intact in non-arteritic CRAO — confirming choroidal perfusion preservation and explaining the cherry red spot
• Choroidal non-perfusion on OCTA in GCA-related CRAO — a critical distinguishing feature
• Useful for non-invasive confirmation when FA cannot be performed (contrast allergy, renal failure, poor patient cooperation)
• Reperfusion monitoring: serial OCTA can document restoration of capillary flow in cases with spontaneous or treatment-induced recanalization

Immediate Ocular Interventions (Within Hours — Limited Evidence)

No ocular intervention for CRAO has been proven to restore vision in a randomised controlled trial. The following measures are widely attempted in the acute setting based on physiological rationale, within the first 1–4 hours. They carry low risk and may provide marginal benefit; however, systemic vascular management is substantially more evidence-based and life-saving.

• Digital ocular massage: Rhythmic pressure on the closed eyelid (5 seconds on, 5 seconds off for 10–15 minutes) creates oscillating IOP changes that may dislodge a lodged embolus distally into a smaller arteriole; most rational within the first 90 minutes; harmless and rapid; efficacy in CRAO is anecdotal
• Anterior chamber paracentesis (AC tap): Withdrawal of 0.1–0.2 mL of aqueous via corneal paracentesis reduces IOP to near-zero, maximising the arteriovenous perfusion pressure gradient; may facilitate embolus movement; performed by an ophthalmologist at the slit lamp; carries low risk of infection and haemorrhage; the strongest available evidence for an ocular intervention in CRAO (case series, not RCT)
• Topical / systemic IOP lowering: Timolol 0.5% drops, acetazolamide 500 mg IV or oral — reduce IOP to improve perfusion pressure; easily administered; low risk; adjunct to other measures
• Hyperbaric oxygen (HBO): Increases dissolved oxygen content of plasma, delivering oxygen to ischaemic retinal tissue despite absent arteriolar flow; requires specialist hyperbaric facility; case series suggest possible benefit if initiated within hours; not standard of care; impractical in most centres
• Carbogen inhalation (95% O₂ + 5% CO₂): CO₂ induces retinal arteriolar vasodilation while O₂ increases tissue oxygenation; experimental; limited clinical availability; not proven in RCT
• Sublingual glyceryl trinitrate (GTN): Vasodilator; used in vasospastic causes (migraine, cocaine); no evidence in embolic CRAO

Thrombolysis — Evidence and Current Status

• Intra-arterial thrombolysis (IACFT) — EAGLE trial: The European Assessment Group for Lysis in the Eye (EAGLE) trial was the largest RCT of intra-arterial thrombolysis (rtPA delivered by catheter into the ophthalmic artery) versus conservative management in acute CRAO; the trial was stopped early due to absence of benefit and higher adverse event rates in the treatment arm; intra-arterial thrombolysis is not recommended as standard care for CRAO
• Systemic intravenous thrombolysis (IV rtPA): Investigated by analogy with ischaemic stroke; small case series and retrospective studies suggest possible visual improvement if administered within 4.5 hours of onset; not yet approved specifically for CRAO and carries risk of systemic haemorrhage; used in some specialist stroke centres as an off-label intervention for acute CRAO when the patient presents within the thrombolytic window; ongoing clinical trials are evaluating IV rtPA in CRAO
• Current guideline position: The American Heart Association/American Stroke Association 2021 guidelines state that IV thrombolysis for CRAO may be considered at comprehensive stroke centres within 4.5 hours of symptom onset, particularly in patients with concurrent cerebral ischaemia — but is not established standard of care; local practice varies significantly between centres

Management of Arteritic CRAO — Giant Cell Arteritis

• IV methylprednisolone 500 mg–1 g daily for 3 days: Initial pulse therapy for acute GCA with sight-threatening complications; reduces vascular inflammation rapidly; prevents contralateral ocular involvement
• Oral prednisolone 1 mg/kg/day (maximum 60 mg): Continued after IV pulse; gradually tapered over 12–24 months guided by symptoms and inflammatory markers (ESR, CRP); do not taper too quickly
• Tocilizumab (IL-6 receptor antagonist, Actemra): Licensed as adjuvant therapy for GCA; the GiACTA trial demonstrated that tocilizumab 162 mg subcutaneous weekly or biweekly significantly increased the rate of sustained remission and reduced cumulative prednisolone dose; recommended in patients who relapse on steroid tapering or who have significant steroid contraindications
• Bone protection: Bisphosphonates (alendronate), calcium 1000 mg/day, vitamin D 800 IU/day — mandatory with long-term steroid therapy to prevent glucocorticoid-induced osteoporosis
• Low-dose aspirin: May reduce ischaemic complications of GCA (meta-analysis data); generally added to steroid therapy in GCA with ophthalmic involvement
• Temporal artery biopsy: Confirms GCA diagnosis; segment >1.5–2 cm from the most symptomatic site; bilateral biopsy may be required if one side is negative in high clinical suspicion; histology shows granulomatous inflammation with giant cells; skip lesions mean a single negative biopsy does not exclude GCA
• Long-term monitoring: Aortic imaging (CT angiography or MR angiography) at 1 year and annually for 5 years to detect large vessel GCA complications (thoracic aortic aneurysm)

Systemic Vascular Management (Non-Arteritic CRAO)

• Antiplatelet therapy: Aspirin 300 mg loading dose then 75–100 mg daily; clopidogrel as alternative; dual antiplatelet (DAPT) for 21 days may be considered per TIA stroke guidelines for high-risk patients; reduces recurrent embolic risk
• Anticoagulation: For confirmed AF, intracardiac thrombus, antiphospholipid syndrome, or other indications; DOACs (apixaban, rivaroxaban, dabigatran) preferred in non-valvular AF; reduces stroke risk by approximately 60–70%
• Carotid endarterectomy (CEA) / carotid artery stenting (CAS): For symptomatic ipsilateral carotid stenosis >70%; ideally within 2 weeks of the embolic event; CEA reduces 5-year stroke risk from ~26% to ~9% in symptomatic high-grade stenosis (NASCET); CAS for high surgical risk patients
• Blood pressure management: Target <130/80 mmHg; long-term antihypertensive therapy is primary and secondary prevention for vascular events
• High-intensity statin therapy: Atorvastatin 80 mg or rosuvastatin 40 mg; target LDL <1.8 mmol/L for secondary prevention; stabilises atheromatous plaques beyond lipid-lowering effects
• Glycaemic control: HbA1c <53 mmol/mol (7.0%) in diabetes; reduces endothelial dysfunction and thrombosis risk
• Smoking cessation: Mandatory lifestyle intervention; refer for pharmacotherapy and behavioural support; reduces ongoing atherosclerosis progression
• PFO closure: Considered in patients under 60 with cryptogenic CRAO and confirmed PFO after multidisciplinary vascular neurology review

Management of Neovascular Complications

• Surveillance for iris/angle neovascularisation: Monthly anterior segment examination with IOP measurement for the first 3–6 months after CRAO; gonioscopy at 6–8 weeks and if IOP rises; detection of iris neovascularisation is an emergency
• Intravitreal anti-VEGF: Immediate injection on detection of rubeosis iridis or angle neovascularisation; rapidly suppresses VEGF and causes regression of new vessels within 24–72 hours; bridges to PRP laser
• Pan-retinal photocoagulation (PRP): Applied to ischaemic retina when neovascularisation is detected; ablates the VEGF-producing ischaemic tissue; combined with anti-VEGF for durable NVG prevention
• Neovascular glaucoma management: Topical and systemic IOP-lowering agents; glaucoma drainage surgery (Ahmed or Baerveldt tube shunt) for refractory NVG; cyclodiode laser for blind painful NVG eyes

Monitoring Schedule

Visual Prognosis — Non-Arteritic CRAO

• Overall visual prognosis is poor: Without treatment, only approximately 25–30% of non-arteritic CRAO eyes recover VA ≥6/60; approximately 30–40% of eyes have final VA of counting fingers or worse; population-based series (Hayreh) consistently demonstrate severe visual disability as the expected outcome in most eyes
• Cilioretinal artery sparing dramatically improves central VA: Eyes with a patent cilioretinal artery supplying the papillomacular bundle may retain 6/12 or better central acuity despite complete CRAO of all other sectors; cilioretinal sparing is the most important favourable prognostic factor and occurs in approximately 15–20% of CRAO eyes
• Spontaneous visual improvement: Partial spontaneous recovery occurs in approximately 20–30% of eyes, typically within the first 1–3 months, from partial thrombus lysis, embolus movement, or collateral flow development; recovery is rarely to 6/12 or better without cilioretinal sparing; minimal recovery beyond 3 months is expected
• Presenting VA predicts outcome: Eyes presenting with VA of counting fingers or worse (no cilioretinal sparing) have a consistently poor prognosis; eyes with VA ≥6/60 at presentation (partial occlusion or cilioretinal sparing) have the best outcomes

Visual Prognosis — Arteritic CRAO (GCA)

• Visual prognosis is very poor in the affected eye: Visual loss in arteritic CRAO is almost always profound and permanent; VA of counting fingers or worse is the expected outcome in the majority of affected eyes even with appropriate steroid therapy, as steroids protect the fellow eye but rarely recover vision in the already-infarcted eye
• Fellow eye risk if untreated: >50% risk of bilateral visual loss in untreated GCA; immediate corticosteroid therapy dramatically reduces (but does not eliminate) this risk; the fellow eye may be protected if steroids are started promptly
• Long-term GCA management: Disease relapse on steroid tapering occurs in approximately 40–50% of GCA patients; tocilizumab significantly reduces relapse rate; ongoing rheumatology follow-up is essential

Favourable Prognostic Factors

• Patent cilioretinal artery supplying the fovea (most important)
• Presenting VA ≥6/60 at the time of assessment
• Early spontaneous embolus movement observed during fundoscopy
• Reperfusion of the CRA demonstrated on FA within the first days
• Vasospasm as the underlying mechanism (most likely to recover)
• Presentation within 1–2 hours of onset (opportunity for acute intervention)

Systemic Prognosis

• Stroke risk: 90-day ischaemic stroke risk 8–12%; highest in the first 7–14 days; risk substantially reduced by antiplatelet/anticoagulant therapy and carotid intervention where indicated; DWI-MRI confirms concurrent cerebral ischaemia in up to 25% at presentation
• Myocardial infarction: 5-year risk elevated approximately 2–3 fold above age-matched controls; reflects shared atherosclerotic burden
• Long-term cardiovascular mortality: Population studies demonstrate significantly elevated 10-year mortality from cardiovascular causes in CRAO patients compared to controls; CRAO is a marker of terminal-stage systemic arteriosclerosis in many patients
• Recurrence: Recurrence of CRAO in the same eye is uncommon (<2% per year) with adequate secondary prevention; fellow eye BRAO or CRAO risk is elevated; ongoing annual ophthalmic review of both eyes is recommended