Central Retinal Vein Occlusion

Primary Mechanism — Occlusion at the Lamina Cribrosa

The central retinal vein and central retinal artery travel together through a narrow fibrous tunnel within the optic nerve at the level of the lamina cribrosa. In CRVO, thrombosis forms within this confined space. The mechanism is mechanistically distinct from BRVO: rather than external arteriovenous crossing compression, CRVO results from a combination of haemodynamic stasis, arterial wall changes compressing the adjacent vein, and local or systemic prothrombotic states — all converging at the single point of maximal anatomical constraint.

• Arteriosclerotic compression: A thickened, rigid central retinal artery (from hypertension-related medial hypertrophy) compresses the adjacent central retinal vein within the shared lamina cribrosa canal, reducing luminal patency and promoting turbulent flow and thrombus formation
• Elevated intraocular pressure: IOP elevation increases the translaminar pressure gradient, compressing the central retinal vein at the lamina cribrosa; glaucoma has a particularly strong association with CRVO and is thought to act directly at this site
• Primary venous thrombosis: Systemic hypercoagulable states (thrombophilia, hyperviscosity) may cause thrombosis within the central retinal vein independent of external compression

Virchow's Triad in CRVO

• Endothelial damage: Chronic hypertension causes endothelial dysfunction in the central retinal vein wall; oxidative stress, inflammatory cytokines, and haemodynamic shear injury at the lamina cribrosa promote prothrombotic endothelial activation
• Stasis: Reduced venous flow velocity due to external compression, low systemic perfusion pressure, or raised IOP diminishes shear-mediated antithrombotic mechanisms; increased blood viscosity (polycythaemia, hyperlipidaemia) worsens stasis
• Hypercoagulability: Systemic thrombophilia (inherited or acquired), oestrogen exposure, inflammatory states, and haematological malignancies create a systemic prothrombotic milieu that facilitates local clot propagation

Less Common Aetiologies

• Inflammatory vasculitis: Behçet disease, sarcoidosis, systemic lupus erythematosus, and other autoimmune conditions cause periphlebitis and inflammatory venous occlusion; important cause of CRVO in younger patients without conventional cardiovascular risk factors
• Myeloproliferative neoplasms: Polycythaemia vera, essential thrombocythaemia — elevated red cell mass and platelet counts cause hyperviscosity and promote thrombosis
• Hyperviscosity syndromes: Multiple myeloma, Waldenström macroglobulinaemia — paraprotein-related plasma viscosity elevation
• Orbital pathology: Orbital cellulitis, thyroid eye disease, orbital tumour — extrinsic compression of the optic nerve can impede central retinal venous drainage
• Optic nerve drusen: Buried drusen in the optic nerve head create structural crowding that may predispose to venous compression at the disc
• Medications: Oral contraceptive pill, hormone replacement therapy, diuretics (haemoconcentration), and certain chemotherapeutic agents increasing thrombotic risk

Step 1 — Complete Venous Obstruction and Pan-Retinal Hypertension

Unlike BRVO which obstructs one quadrant's drainage, CRVO occludes the single outflow vessel for the entire retinal venous system. Venous pressure rises globally throughout all four quadrants, forcing hydrostatic extravasation of erythrocytes, plasma proteins, and lipids through severely stressed capillary walls. The resulting haemorrhages appear in all four retinal quadrants simultaneously, often extending to the mid-periphery and beyond. Superficial haemorrhages follow nerve fibre layer architecture (flame-shaped); deeper haemorrhages are dot-and-blot in pattern and indicate involvement of the inner nuclear and outer plexiform layers.

Step 2 — Optic Nerve Head Oedema

The optic disc itself is affected by retrograde venous congestion. Axoplasmic transport is disrupted at the disc level, and venous stasis directly causes disc swelling with blurring of the disc margins. This is one of the distinguishing features of CRVO versus BRVO — disc oedema is virtually universal in CRVO, whereas it is inconstant and milder in BRVO. The degree of disc oedema correlates imperfectly with severity but is a useful clinical marker of active occlusion.

Step 3 — VEGF Upregulation and Blood-Retinal Barrier Breakdown

Widespread retinal ischaemia triggers massive upregulation of VEGF-A and related angiogenic factors. VEGF disrupts tight junctions of the inner blood-retinal barrier (retinal vascular endothelium) and the outer blood-retinal barrier (retinal pigment epithelium), causing a global increase in retinal vascular permeability. The clinical consequence is cystoid macular oedema — fluid accumulating in the outer plexiform and inner nuclear layers of the fovea — which is the primary driver of visual loss. In severe ischaemic CRVO, subretinal fluid may also develop, elevating the neurosensory retina at the fovea.

Step 4 — Anterior Segment Neovascularisation and Neovascular Glaucoma

In ischaemic CRVO, the massive sustained VEGF load — far greater than in BRVO — diffuses forward through the vitreous to reach the iris and trabecular meshwork. This drives neovascularisation of the iris (rubeosis iridis) and the anterior chamber angle (neovascular angle), ultimately causing progressive synechial angle closure and intractable IOP elevation: neovascular glaucoma (NVG). The classic "100-day" timeline reflects the average time from CRVO onset to clinically apparent angle neovascularisation, though onset may occur earlier (as early as 4–6 weeks) or later.

Step 5 — Natural Resolution and Collateral Formation

In non-ischaemic CRVO, partial recanalisation of the thrombus may occur over weeks to months. Optociliary shunt vessels (chorioretinal collaterals) may develop at the disc, providing an alternative drainage route from the retinal venous system into the choroidal circulation. These collaterals appear as dilated, non-leaking vessels around the disc on FA and are a marker of chronic venous obstruction. Their presence does not guarantee visual recovery but may accompany gradual oedema resolution.

Primary Classification — Ischaemic vs Non-Ischaemic CRVO

The most clinically important classification, established by Hayreh (1994) and adopted by the CRVO Study Group, divides CRVO into perfused (non-ischaemic) and non-perfused (ischaemic) subtypes based on clinical, electrophysiological, and angiographic criteria. This distinction drives all management decisions, particularly the urgency of monitoring for anterior segment neovascularisation.

Hayreh's Extended Classification

• Non-ischaemic (perfused) CRVO: Majority; favourable outcome; risk of conversion to ischaemic requires monitoring every 4–6 weeks for the first 6 months
• Ischaemic (non-perfused) CRVO: Minority but causes most serious complications; NVG risk mandates monthly IOP and anterior segment examination; intravitreal anti-VEGF ± PRP typically required
• Indeterminate CRVO: Haemorrhages too dense at presentation for adequate FA assessment; reclassify when haemorrhages partially resolve (6–10 weeks); treat as ischaemic until proven otherwise

Hemispheric (Hemicentral) Retinal Vein Occlusion

A distinct variant in which a dual-trunk central retinal vein (a normal anatomical variant in approximately 20% of eyes) undergoes occlusion of one trunk, producing haemorrhages and oedema confined to the superior or inferior hemisphere. Clinical appearance mimics CRVO in one half of the fundus. Management follows CRVO protocols. The visual prognosis of hemispheric RVAO lies between BRVO and CRVO.

Ocular Risk Factors

• Raised intraocular pressure / open-angle glaucoma: The most important ocular risk factor; glaucoma is present in 10–20% of CRVO patients compared to ~2% in the general population; elevated IOP compresses the central retinal vein at the lamina cribrosa; even borderline IOP elevation (18–21 mmHg) significantly increases CRVO risk
• Optic disc drusen: Structural crowding of the optic nerve head creates vulnerability to venous compression; CRVO in young patients should prompt optic nerve head evaluation for buried drusen
• High axial myopia: Associated with reduced orbital venous drainage and structural optic nerve changes that may predispose to CRV compression
• Previous BRVO in the same eye: Indicates underlying arteriosclerosis that puts the CRV at risk

Systemic Cardiovascular Risk Factors

• Systemic hypertension: Present in 60–70% of CRVO patients; promotes arteriosclerosis of the central retinal artery, compressing the adjacent vein; the most important modifiable systemic risk factor
• Hyperlipidaemia: Contributes to arteriosclerosis and endothelial dysfunction; dyslipidaemia is present in up to 30% of CRVO patients
• Diabetes mellitus: Promotes endothelial dysfunction, hypercoagulability, and hyperviscosity; less strongly associated with CRVO than with BRVO but remains an important co-morbidity
• Obesity and metabolic syndrome: Pro-inflammatory, pro-thrombotic state; adipokine-mediated endothelial dysfunction
• Cardiovascular disease: Atherosclerosis is a shared pathological substrate; CRVO patients have elevated rates of coronary artery disease and cerebrovascular disease

Haematological and Thrombophilic Risk Factors

• Thrombophilia (particularly in young patients): Factor V Leiden mutation, prothrombin G20210A, protein C/S deficiency, antithrombin III deficiency — screen all patients under 50 without conventional risk factors
• Antiphospholipid syndrome: Lupus anticoagulant and anti-cardiolipin antibodies create a strong hypercoagulable state; high recurrence risk; requires anticoagulation
• Hyperhomocysteinaemia: Elevated plasma homocysteine damages endothelium and promotes thrombosis; correctable with folate, B6, and B12 supplementation
• Hyperviscosity: Polycythaemia vera, essential thrombocythaemia, multiple myeloma, leukaemia — increased whole blood viscosity from cellular or plasma protein excess
• Dehydration: Haemoconcentration increases whole blood viscosity; acute illness, diuretic overuse, and poor fluid intake are precipitating factors particularly in elderly patients
• Oral contraceptive pill / HRT: Oestrogen-mediated activation of coagulation factors; particularly important risk in young women with otherwise unexplained CRVO

Demographic Risk Factors

• Age: Incidence rises with age; peak in the seventh and eighth decade; but CRVO in young adults (<50 years) is not uncommon and warrants extensive thrombophilia workup
• Sex: Approximately equal in older patients; in younger patients, oestrogen-related and autoimmune causes are more common in women
• Ethnicity: Asian populations may have a higher age-adjusted incidence, possibly reflecting higher rates of hypertension and angle-closure–related IOP elevation

Funduscopic Signs — Acute Phase

• Diffuse flame-shaped haemorrhages in all four quadrants: The pathognomonic feature of CRVO; haemorrhages are located in the nerve fibre layer and follow the arcuate course of retinal nerve fibres; they extend from the disc to the mid-periphery and beyond; the density and distribution reflect the severity of the occlusion
• Markedly dilated and tortuous veins: All four major branch veins appear engorged, dark, and tortuous throughout their entire course from the disc to the periphery; this distinguishes CRVO from BRVO (where only one branch vein is affected) and from other conditions
• Disc oedema (papilloedema-like appearance): Virtually universal in acute CRVO; the disc margins are blurred and elevated due to venous congestion and axoplasmic stasis at the disc; the peripapillary nerve fibre layer is oedematous; may have peripapillary haemorrhages "splashing" around the disc
• Cotton wool spots (CWS): Superficial white fluffy lesions indicating ischaemic axoplasmic stasis; number and distribution reflect the degree of retinal ischaemia; more numerous CWS suggest ischaemic rather than non-ischaemic CRVO; typically resolve within 6–8 weeks
• Dot and blot haemorrhages (deeper layers): In addition to superficial flame haemorrhages, deeper intraretinal haemorrhages within the inner nuclear and outer plexiform layers indicate more severe venous hypertension and capillary disruption

Macular Signs

• Cystoid macular oedema (CMO): Present in the majority of CRVO eyes; intraretinal fluid accumulates in the outer plexiform and inner nuclear layers forming hyporeflective cysts on OCT; foveal elevation may be massive in severe cases; the primary target of anti-VEGF therapy
• Subretinal fluid (SRF): More common in CRVO than BRVO; indicates failure of outer blood-retinal barrier; elevation of the neurosensory retina at the fovea; may contribute to metamorphopsia and reduced VA independent of cystoid oedema
• Hard exudates: Lipid deposits at the margins of resolving oedema; a sign of chronic or recurrent macular leakage; threatening foveal involvement is a sign of longstanding disease
• Macular haemorrhage: Intraretinal or preretinal haemorrhage directly overlying the fovea; associated with poor prognosis and prolonged recovery
• Macular ischaemia: Capillary dropout around the foveal avascular zone; detectable on FA and OCTA; most important determinant of final visual acuity ceiling; not treatable with any current modality

Anterior Segment Signs

• Relative afferent pupillary defect (RAPD): A key bedside sign; present in ischaemic CRVO reflecting extensive inner retinal ischaemia; the swinging flashlight test showing a RAPD of >0.9 log units is 95% sensitive for ischaemic CRVO in the context of CRVO diagnosis
• Rubeosis iridis (iris neovascularisation): Pathological new vessels on the iris surface, typically beginning at the pupillary margin and progressing to the angle; appears as fine red vessels on the anterior surface of the iris; requires urgent slit-lamp examination with dilation in all ischaemic CRVO patients; constitutes an ocular emergency
• Angle neovascularisation: New vessels in the trabecular meshwork visible on gonioscopy; precedes clinically apparent iris neovascularisation and is a critical finding that mandates immediate treatment
• Elevated intraocular pressure: May be present as a risk factor for CRVO; when IOP elevation develops after CRVO diagnosis, it indicates progressive angle closure from neovascular glaucoma
• Corneal oedema: In severe neovascular glaucoma with IOP >40–50 mmHg, corneal oedema (Haab's striae pattern) may develop, causing reduced corneal clarity and pain

Chronic Phase Signs

• Optociliary shunt vessels: Dilated, non-leaking collateral channels at the disc connecting retinal venous circulation to the choroidal venous system; a marker of longstanding venous obstruction; their appearance may correlate with partial spontaneous improvement in macular oedema
• Disc pallor / optic atrophy: Following severe ischaemic CRVO, the optic disc may become pale, indicating loss of retinal ganglion cells; portends permanent visual loss
• Epiretinal membrane: A frequent sequela; fibrocellular proliferation on the inner retinal surface; produces metamorphopsia and may maintain chronic macular oedema despite successful anti-VEGF treatment
• RPE atrophy / macular scarring: End-stage change from chronic oedema and ischaemia; associated with final VA of CF or worse

Visual Symptoms

• Sudden painless visual loss: The cardinal presenting symptom; onset is typically acute, occurring over hours; severity ranges from mild blurring to profound visual loss (counting fingers or hand motion only) depending on ischaemic status and macular involvement; absence of pain distinguishes CRVO from acute angle closure glaucoma and other painful causes of sudden visual loss
• Diffuse visual field constriction or altitudinal defect: Corresponding to the global haemorrhage and ischaemia; patients may notice reduced peripheral vision or a haze over the visual field rather than a focal scotoma (unlike BRVO, which typically causes a sectoral field defect)
• Central scotoma: Blurring or loss of central vision from macular oedema; patients describe difficulty reading, recognising faces, and performing close-up tasks; may be described as a smudge or fog in the centre of vision
• Metamorphopsia: Distortion of straight lines and images caused by photoreceptor displacement from macular oedema; Amsler grid testing confirms and monitors this symptom
• Dyschromatopsia: Colour desaturation or red-green/blue-yellow colour deficiency arising from inner retinal ischaemia; particularly in ischaemic CRVO; may persist as a chronic symptom
• Floaters and sudden dense visual loss (vitreous haemorrhage): Sudden onset floaters or a dramatic red or black obscuration of vision indicates vitreous haemorrhage from neovascularisation; constitutes an emergency

Symptoms of Neovascular Glaucoma

• Painful red eye: When NVG develops with very high IOP (>40 mmHg), patients experience ocular pain, periorbital aching, and a red injected eye; this is often confused with acute angle closure glaucoma but arises on the background of known CRVO
• Haloes around lights: Corneal oedema from raised IOP causes diffraction haloes; in the context of CRVO, this is an alarming sign of impending NVG
• Nausea and vomiting: Severe IOP elevation (as in NVG) can trigger a vagal response with nausea, vomiting, and headache, mimicking a systemic illness; critically important to check IOP in any CRVO patient presenting with these symptoms

Neovascular Glaucoma — The Most Feared Complication

Neovascular glaucoma (NVG) is the most serious complication of ischaemic CRVO and the primary driver of irreversible vision loss and ocular morbidity. Historically, NVG occurred in approximately 50% of ischaemic CRVO eyes within the first 90–100 days — a timeline so consistent it earned the disease its colloquial name, "100-day glaucoma." Modern anti-VEGF therapy has substantially reduced this incidence when initiated early.

• Mechanism: Sustained VEGF production from ischaemic retina diffuses into the anterior segment, driving neovascularisation of the iris and trabecular meshwork; fibrovascular membrane causes progressive synechial angle closure; once synechiae form, IOP elevation becomes permanent
• Clinical stages: (1) Pre-rubeosis: angle neovascularisation on gonioscopy only; (2) Rubeosis iridis: visible iris new vessels; (3) Open-angle NVG: elevated IOP with open but dysfunctional angle; (4) Closed-angle NVG: synechial closure — most difficult to manage
• Consequences: Intractable IOP elevation requiring multiple IOP-lowering agents; corneal decompensation; optic atrophy; visual acuity loss to no perception of light (NPL); severe ocular pain; may require cyclodiode laser or evisceration in end-stage disease

Macular Complications

• Chronic cystoid macular oedema: Persistent oedema beyond 3–6 months progressively destroys photoreceptors and RPE; irreversible once outer retinal structures are lost; the principal target of treatment
• Macular ischaemia: FAZ enlargement due to capillary dropout around the macula; creates a fixed ceiling on visual recovery regardless of treatment; present in the majority of ischaemic CRVO eyes and in some non-ischaemic eyes
• Epiretinal membrane formation: Occurs in approximately 25–30% of CRVO eyes; causes persistent distortion and may maintain chronic CMO despite anti-VEGF therapy; requires vitrectomy with membrane peeling if significant
• Macular hole: Uncommon; lamellar or full-thickness macular holes may develop from chronic tractional forces associated with ERM or vitreoretinal traction; requires vitrectomy
• Retinal pigment epithelium atrophy: End-stage decompensation of RPE from chronic oedema and ischaemia; associated with visual acuity of counting fingers or worse; no effective treatment at this stage

Posterior Segment Neovascular Complications

• Vitreous haemorrhage: Rupture of NVD or NVE from ischaemic retinal neovascularisation; presents with sudden vision loss; if dense and non-clearing within 1–3 months, vitrectomy is required
• Tractional retinal detachment: Fibrovascular proliferation from NVD/NVE may cause progressive traction on the retina; requires complex vitreoretinal surgery; visual outcome poor
• Optic atrophy: Chronic venous obstruction and ischaemia cause irreversible ganglion cell loss; optic pallor is a permanent marker of established damage; associated with permanent visual field loss

Fellow Eye and Systemic Complications

• Fellow eye CRVO: Approximately 7–10% of patients develop CRVO in the fellow eye within 5 years; particularly if systemic risk factors are not adequately controlled
• Fellow eye BRVO: Arteriosclerosis in the fellow eye puts branch veins at risk; fellow eye fundus examination should be performed at every visit
• Cardiovascular events: CRVO is a recognised marker of systemic vascular disease; significantly elevated long-term risk of myocardial infarction and stroke

Hypertension and Cardiovascular Disease

• Systemic hypertension: Present in 60–70% of CRVO patients; frequently undiagnosed or inadequately controlled at the time of presentation; CRVO may be the first clinical manifestation of long-standing hypertension; urgent BP measurement and GP referral is mandatory
• Coronary artery disease: Atherosclerosis is a shared pathology; CRVO patients have approximately 2–3 times the age-matched risk of myocardial infarction
• Cerebrovascular disease: Shared small vessel arteriosclerotic disease; CRVO has been associated with cerebral white matter lesions on MRI; elevated risk of lacunar stroke; carotid duplex scanning is recommended in all CRVO patients to exclude significant carotid artery stenosis
• Peripheral arterial disease: Atherosclerotic burden is not confined to the eye; ankle-brachial pressure index assessment may be warranted in patients with multiple vascular risk factors

Metabolic and Endocrine Associations

• Diabetes mellitus: Endothelial dysfunction and hypercoagulable state; screen all CRVO patients with fasting glucose and HbA1c; diabetic retinopathy may coexist, complicating fundus interpretation
• Hyperlipidaemia: Atherogenic dyslipidaemia (high LDL, low HDL, high triglycerides) is highly prevalent in CRVO patients; statin therapy may be indicated for cardiovascular risk reduction
• Hypothyroidism: Causes hyperlipidaemia and hypercoagulable state; thyroid function should be checked in CRVO patients with unexplained hyperlipidaemia or cardiovascular risk factors
• Obesity and metabolic syndrome: Central adiposity, hypertriglyceridaemia, low HDL, hypertension, and impaired fasting glucose as a cluster substantially amplify CRVO risk

Haematological and Autoimmune Associations

• Thrombophilias: Factor V Leiden (commonest inherited thrombophilia, ~5% prevalence in Caucasians); prothrombin gene mutation; protein C/S/antithrombin deficiency — screen all patients under 50 and those with recurrent or bilateral occlusions
• Antiphospholipid syndrome (APS): A major cause of CRVO in younger patients; bilateral CRVO or recurrent venous occlusions should prompt APS screening; anticoagulation (warfarin) is indicated if APS is confirmed
• Myeloproliferative neoplasms: Polycythaemia vera — elevated haematocrit increases viscosity; essential thrombocythaemia — abnormal platelet function and thrombocytosis; venesection or cytoreduction may prevent recurrence
• Multiple myeloma and Waldenström macroglobulinaemia: Paraprotein-mediated hyperviscosity; plasmapheresis may be indicated acutely; haematology referral essential
• Systemic vasculitis (SLE, Behçet, sarcoidosis, GCA): Inflammatory periphlebitis; particularly in younger patients; serological and clinical evaluation for systemic inflammatory disease is important

Clinical Diagnosis

CRVO is a clinical diagnosis based on the combination of characteristic funduscopic findings: diffuse flame haemorrhages in all four quadrants, markedly dilated tortuous veins throughout, disc oedema, and cotton wool spots — in the setting of appropriate symptoms and risk factors. No additional imaging is required for the diagnosis itself, but multimodal imaging is essential for classification (ischaemic vs non-ischaemic), staging severity, planning treatment, and monitoring response.

• Best-corrected visual acuity (BCVA): The most important baseline clinical measurement and principal treatment endpoint; VA on presentation is the strongest independent predictor of final visual outcome
• Pupil examination — RAPD: The swinging flashlight test for a relative afferent pupillary defect is a critical bedside test; a significant RAPD strongly suggests ischaemic CRVO and guides urgency of FA
• Intraocular pressure: Mandatory measurement at every visit; elevated IOP is both a risk factor for CRVO and an early warning sign of developing NVG; asymmetric IOP elevation in the CRVO eye should prompt gonioscopy
• Anterior segment slit-lamp examination: Careful iris examination for fine neovascular vessels (rubeosis iridis) at the pupillary margin and within the iris stroma; gonioscopy to examine the trabecular meshwork for angle neovascularisation
• Colour fundus photography: Non-mydriatic or mydriatic fundus camera imaging for baseline documentation; serial fundus photography allows monitoring of haemorrhage absorption, collateral formation, neovascularisation, and disc changes

Optical Coherence Tomography (OCT)

• Central subfield thickness (CST): The primary quantitative metric for macular oedema; CST >300 µm (or >250 µm in some protocols) typically guides initiation and continuation of anti-VEGF treatment; serial CST measurements guide retreatment in treat-and-extend (TAE) and PRN protocols
• Intraretinal cysts (IRC): Hyporeflective cystic spaces in the inner nuclear and outer plexiform layers; the characteristic OCT finding in CRVO-associated CMO; large, coalescent cysts indicate severe oedema; persistent cysts are associated with outer retinal damage
• Subretinal fluid (SRF): Fluid between the neurosensory retina and RPE; more common in CRVO than BRVO; indicates breakdown of the outer blood-retinal barrier; some studies suggest SRF correlates with preserved photoreceptor viability (controversial)
• Ellipsoid zone (IS/OS) integrity: The most critical prognostic OCT biomarker; intact IS/OS lines indicate viable photoreceptors and predict better VA recovery; disruption or loss of the EZ indicates irreversible photoreceptor damage and a ceiling on VA improvement
• Outer nuclear layer (ONL) thickness: Progressive ONL thinning represents cumulative photoreceptor loss from chronic oedema; a thin ONL at baseline predicts poor visual prognosis
• Disorganisation of inner retinal layers (DRIL): Loss of distinct boundaries between inner retinal layers on OCT cross-section; a marker of inner retinal ischaemia; associated with worse VA outcomes independent of oedema resolution
• Epiretinal membrane: Hyperreflective band on the inner retinal surface; may be causing or contributing to CMO; important to identify as it may require surgical treatment independent of oedema management

Fluorescein Angiography (FA)

• Perfusion assessment — ischaemic vs non-ischaemic classification: The most important role of FA in CRVO; extensive capillary dropout ≥10 disc areas = ischaemic CRVO; FA is ideally performed once haemorrhages have partially cleared (4–8 weeks from onset) as dense haemorrhages block fluorescence and prevent perfusion assessment
• Arteriovenous transit time: Prolonged AV transit time (from arterial filling to venous phase) reflects degree of venous obstruction; normally 11–12 seconds; significantly prolonged in CRVO
• Optic disc leakage: Hyperfluorescence from disc oedema; extensive disc staining implies severe venous obstruction; fades as the disc oedema resolves
• Macular leakage: Late hyperfluorescence at the macula confirming active CMO; guides retreatment decisions alongside OCT CST
• FAZ assessment: Enlargement of the foveal avascular zone indicates macular ischaemia; a large FAZ (>600 µm) portends poor visual prognosis regardless of oedema treatment
• NVD / NVE leakage: Hyperfluorescence and frank dye leakage from disc or retinal new vessels; mandates urgent scatter PRP
• Optociliary shunts: Non-leaking, patent collateral vessels at the disc; confirm chronicity; their non-leakage distinguishes them from NVD

OCT Angiography (OCTA)

• Non-invasive, depth-resolved capillary flow imaging; allows quantification of FAZ size and capillary plexus dropout in superficial and deep capillary plexuses without dye injection
• Deep capillary plexus (DCP) involvement is particularly prognostically significant and correlates with worse visual outcomes
• Does not show active leakage or confirm neovascularisation activity — FA remains necessary for these assessments
• Useful for serial monitoring of macular ischaemia progression and for pre-treatment assessment

Electroretinography (ERG)

Pattern or full-field ERG may be used to classify ischaemic versus non-ischaemic CRVO, particularly when FA is technically difficult (dense haemorrhages). A b-wave amplitude reduction of ≥75% compared to the fellow eye is diagnostic of ischaemic CRVO. ERG is not routinely performed in all centres but is a recognised tool in the CRVO Study Group diagnostic criteria.

Macular Oedema — First-Line: Intravitreal Anti-VEGF

Anti-VEGF therapy is the current standard of care for macular oedema in CRVO, supported by high-quality randomised controlled trial evidence from the CRUISE (ranibizumab) and COPERNICUS/GALILEO (aflibercept) trials. Anti-VEGF agents simultaneously reduce macular oedema (by blocking VEGF-mediated permeability) and suppressing the ischaemic drive to anterior segment neovascularisation, making them particularly valuable in ischaemic CRVO.

• Ranibizumab (Lucentis) 0.5 mg: CRUISE trial — mean VA gain of +14.9 ETDRS letters at 6 months (ranibizumab 0.5 mg) vs. +0.8 letters (sham); significant CST reduction; monthly dosing in the loading phase; TAE or PRN thereafter; licensed for CRVO-related CMO
• Aflibercept (Eylea) 2 mg: COPERNICUS trial — 60.2% of aflibercept-treated eyes gained ≥15 letters at 24 weeks vs. 22.2% sham; GALILEO trial confirmed efficacy; licensed for CRVO-related CMO; monthly for 6 doses, then every 2 months; broad VEGF-trap mechanism (VEGF-A, VEGF-B, PlGF)
• Bevacizumab (Avastin) 1.25 mg: Off-label; widely used globally due to cost; non-inferior to ranibizumab in multiple comparative studies; same anti-VEGF-A mechanism; acceptable for cost-sensitive healthcare settings
• Faricimab (Vabysmo) 6 mg: Dual-pathway inhibitor (anti-VEGF-A and anti-Ang-2); emerging evidence for CRVO; may allow extended treatment intervals; may offer advantages in treatment burden reduction
• Dosing strategy: 6 monthly loading injections (or until dry retina), followed by TAE extending intervals by 2–4 weeks per visit if stable; retreatment triggered by OCT CST increase or VA loss; CRVO typically requires more injections and longer treatment duration than BRVO

Macular Oedema — Second Line: Intravitreal Corticosteroids

• Dexamethasone intravitreal implant (Ozurdex, 0.7 mg): Biodegradable implant releasing sustained-release dexamethasone over ~4–6 months; GENEVA trial demonstrated VA gain in CRVO; particularly useful for anti-VEGF non-responders, patients who cannot attend for frequent injections, pseudophakic patients, and those with predominantly inflammatory aetiology; main risks: cataract acceleration in phakic eyes and IOP elevation (>10 mmHg in ~30%; typically responsive to topical agents but requires monitoring)
• Triamcinolone acetonide (IVTA, 4 mg): Off-label; shorter duration than Ozurdex (2–3 months); SCORE trial demonstrated non-inferiority to standard care for non-ischaemic CRVO but high IOP and cataract risk limit its use; largely superseded by Ozurdex and anti-VEGF agents
• Fluocinolone acetonide intravitreal implant (Iluvien, 190 μg): Ultra-long-acting (up to 36 months) corticosteroid implant; emerging evidence in chronic refractory CMO from CRVO; significant cataract and IOP risks; reserved for recalcitrant cases

Pan-Retinal Photocoagulation (PRP)

• Indication: Anterior or posterior segment neovascularisation (rubeosis iridis, angle NV, NVD, NVE) in the context of ischaemic CRVO; destroys ischaemic retina to eliminate the VEGF stimulus driving neovascularisation; does NOT treat macular oedema and may transiently worsen it
• Timing: Once ischaemic CRVO is confirmed on FA and/or rubeosis is detected; often performed concurrently with anti-VEGF injection — anti-VEGF provides rapid VEGF suppression while PRP provides durable structural ablation
• CRVO Study Group finding: Prophylactic PRP in ischaemic CRVO without neovascularisation does NOT prevent NVG; prophylactic PRP is not indicated — only treat when neovascularisation is present or imminent
• Peripheral retinal ablation extent: 1,200–2,000 burns (500 μm spot size, 0.1 sec duration) applied to the peripheral retina in 2–3 sessions; the extent is tailored to the FA-confirmed non-perfused area

Management of Neovascular Glaucoma

• Step 1 — Immediate anti-VEGF: Intravitreal anti-VEGF injection causes rapid regression of iris and angle neovascularisation (within 24–72 hours); this buys time for PRP to exert its structural effect; anti-VEGF alone does not provide durable control — PRP is mandatory
• Step 2 — PRP: Applied as soon as the media allows (anti-VEGF may first be used to reduce iris engorgement and improve visualisation); laser applied to all ischaemic retina to eliminate the VEGF drive
• Step 3 — IOP management: Topical IOP-lowering agents (prostaglandins, beta-blockers, carbonic anhydrase inhibitors, alpha-agonists); oral acetazolamide in acute IOP spikes; once synechial closure is established, medical management alone is insufficient
• Step 4 — Surgical IOP control (if medical management fails): Glaucoma drainage device (Ahmed or Baerveldt tube shunt) — preferred in NVG; trabeculectomy — high bleb failure rate in NVG; cyclodiode (trans-scleral cyclophotocoagulation) — for refractory NVG or eyes with poor visual prognosis; reserved for pain management in blind eyes

Surgical Management

• Pars plana vitrectomy (PPV): Indicated for dense non-clearing vitreous haemorrhage (>1–3 months), tractional retinal detachment, or vitreoretinal traction contributing to chronic CMO; intraoperative endolaser PRP applied during vitrectomy; may also allow ILM peeling for ERM-related persistent CMO
• Radial optic neurotomy (RON): A surgical procedure involving incision of the scleral ring at the optic nerve head to decompress the central retinal vein at the lamina cribrosa; investigated in multiple case series with variable results; no RCT evidence; not standard of care; largely abandoned due to risk of visual field loss from nerve fibre damage
• Endovascular thrombolysis / tissue plasminogen activator (tPA): Experimental; no approved role in routine CRVO management; risk-benefit ratio unfavourable compared to anti-VEGF

Systemic Risk Factor Management

Monitoring Protocol

Visual Outcome — Non-Ischaemic CRVO

• Anti-VEGF era outcomes: CRUISE trial (ranibizumab) — mean VA gain of +14.9 ETDRS letters at 6 months for the 0.5 mg group; 47% gained ≥15 letters; GALILEO trial (aflibercept) — 60% gained ≥15 letters at 24 weeks; outcomes substantially superior to natural history or laser treatment
• Natural history (without treatment): Approximately 25–30% of non-ischaemic CRVO eyes recover 6/12 or better spontaneously within 12 months; however, functional recovery is unpredictable and waiting for spontaneous improvement risks prolonged photoreceptor damage that limits later treatment response
• Long-term prognosis: 30–40% of initially non-ischaemic CRVO eyes develop persistent CMO requiring ongoing treatment for >2 years; treatment burden (injection frequency) is typically greater for CRVO than BRVO; some patients require monthly injections indefinitely

Visual Outcome — Ischaemic CRVO

• Poor overall prognosis: Macular ischaemia creates an insurmountable ceiling on visual recovery; even with successful anatomical resolution of oedema, VA may remain at 6/60 or worse if the FAZ is significantly enlarged or the ellipsoid zone is disrupted
• Risk of NVG: Historically 50%; with monthly anti-VEGF monitoring and treatment, this has been substantially reduced but not eliminated; NVG, once established with synechial angle closure, carries a risk of VA <6/60 from optic nerve damage
• VA at presentation: The most powerful predictor of final outcome; VA <6/60 at presentation in ischaemic CRVO is associated with final VA <6/60 in approximately 60% of cases even with optimal treatment

Negative Prognostic Factors

• Ischaemic CRVO classification (≥10 DA non-perfusion on FA)
• Presenting VA <6/60 (counting fingers or worse)
• Significant RAPD at presentation (>0.9 log units)
• ERG b-wave reduction ≥75% at baseline
• Disruption or absence of the ellipsoid zone (IS/OS) on OCT
• FAZ enlargement >600 µm on FA or OCTA
• DRIL (disorganisation of inner retinal layers) on OCT
• ONL thinning at baseline
• Delay to treatment >6 months from symptom onset
• Development of neovascular glaucoma with synechial angle closure
• Epiretinal membrane causing persistent CMO
• Bilateral CRVO (may indicate severe systemic disease)

Recurrence and Fellow Eye Risk

• Recurrence in the same eye: Uncommon (<5%) if systemic risk factors are adequately controlled; recurrence in the same eye is an indication for more thorough thrombophilia and systemic cardiovascular evaluation
• Fellow eye involvement: CRVO in the fellow eye occurs in approximately 7–10% of patients within 5 years; fellow eye BRVO is also significantly elevated; both eyes require ongoing annual monitoring
• Long-term cardiovascular mortality: Studies show a 3–5 year cardiovascular mortality of approximately 20% in CRVO patients, consistent with the high systemic vascular risk burden; aggressive risk factor modification is a life-saving, not merely sight-saving, intervention