Retinal vein and artery occlusions

Central Retinal Vein Occlusion (CRVO)

Central retinal vein occlusion is the second most prevalent vision-threatening retinal vascular pathology worldwide, trailing only diabetic retinopathy. CRVO characteristically impacts older adults in their sixth to eighth decades, driven by systemic cardiovascular risk factors and localized anatomical vulnerabilities.

Pathogenesis: Virchow's Triad at the Lamina Cribrosa

The pathogenesis of CRVO is governed by the principles of Virchow's Triad (haemodynamic stasis, endothelial injury, and hypercoagulability) acting at a unique anatomical bottleneck:

1. Anatomical Confinement: The central retinal artery and central retinal vein pass together through a narrow, rigid aperture within the fibrous ring of the lamina cribrosa of the sclera, where they share a common adventitial connective tissue sheath.
2. Mechanical Compression & Stasis: In individuals with systemic hypertension or arteriosclerosis, atheromatous thickening and sclerosis of the relatively thick-walled central retinal artery compresses the thin-walled, compliant central retinal vein against the unyielding scleral rim of the lamina cribrosa. This compression causes luminal stenosis, creating turbulent blood flow, localized haemodynamic stasis, and secondary endothelial shear damage.
3. Thrombus Formation: Endothelial denudation exposes subendothelial collagen, triggering platelet aggregation, tissue factor release, and secondary intraluminal thrombus formation, totally or sub-totally occluding venous outflow.

Non-Ischaemic vs. Ischaemic CRVO

CRVO manifests as a clinical spectrum divided into two distinct functional and prognostic entities:

Systemic Evaluation in CRVO

Review blood pressure, glucose, lipid and cardiovascular risk, smoking, medications and glaucoma. History and examination may suggest a hyperviscosity, inflammatory or haematological disorder requiring targeted assessment. A young age or bilateral disease can justify further investigation, but routine inherited-thrombophilia or MTHFR panels are not indicated for every young patient. Tests should change management and be coordinated with the appropriate physician. Anticoagulation is not routine treatment for the ocular oedema of RVO.

Evidence-Based Management of CRVO

1. Intravitreal Anti-VEGF Pharmacotherapy

Intravitreal anti-VEGF represents the first-line standard of care for macular oedema secondary to CRVO:

• CRUISE Trial (Ranibizumab): Evaluated monthly ranibizumab (0.3 mg and 0.5 mg) vs. sham injection. At 6 months, patients receiving ranibizumab 0.5 mg gained a mean of +14.9 letters (compared to +0.8 letters with sham), with 47.7% gaining $\ge 15$ letters.
• COPERNICUS and GALILEO Trials (Aflibercept): Evaluated monthly intravitreal aflibercept 2.0 mg vs. sham. At 24 weeks, aflibercept-treated eyes achieved extraordinary visual improvements of +17.3 to +18.0 letters, with over 56% to 60% gaining $\ge 15$ letters.

2. Intravitreal Corticosteroids

• GENEVA Trial (Dexamethasone 0.7 mg Implant): Demonstrated that a single biodegradable dexamethasone implant (Ozurdex) produced rapid, statistically significant visual gains ($\ge 15$ letters in ~30% of eyes at day 60). It serves as an outstanding second-line agent or primary choice in pseudophakic patients, vitrectomised eyes, or individuals unable to maintain monthly anti-VEGF injection schedules.

3. The Role of Panretinal Photocoagulation (CVOS Findings)

The landmark Central Vein Occlusion Study (CVOS) tested whether prophylactic panretinal photocoagulation (PRP) in ischaemic CRVO could prevent neovascular glaucoma:

Branch Retinal Vein Occlusion (BRVO)

Branch retinal vein occlusion is approximately three times more common than CRVO, typically presenting with acute, painless, sectoral visual field loss or blur.

Anatomical Predilection and Arteriovenous Crossings

BRVO often arises at an arteriovenous crossing where the artery lies anterior to the vein and shared adventitial tissue can contribute to venous compression. This disease-associated arrangement does not mean arteries are anterior at more than 99% of all normal crossings.

1. Mechanical Constriction: Arteriolosclerosis and chronic hypertensive thickening of the rigid arteriolar wall compress the underlying, thin-walled compliant venule against the deep retinal tissue.
2. Superotemporal predilection: BRVO commonly involves the superotemporal arcade, reflecting the distribution of vulnerable arteriovenous crossings; location alone does not establish perfusion or visual prognosis.
3. Fundus Appearance: A sharply demarcated, wedge-shaped or fan-shaped distribution of flame and blot intraretinal haemorrhages, retinal oedema, and cotton-wool spots extending outward from the offending A/V crossing point, with its apex pointing toward the blockage.

Complications and Landmark Trials in BRVO

• Macular oedema: A major cause of sustained central loss. BRAVO compared ranibizumab with sham, whereas VIBRANT compared aflibercept with grid laser. Anti-VEGF is commonly a first-line option; choice incorporates anatomy, lens, pressure, contraindications and visit burden rather than a claim that both trials used a laser comparator.
• Retinal neovascularisation: Ischaemic retina increases risk. Look for retinal/disc new vessels and vitreous haemorrhage; nonperfusion alone does not automatically require sector laser.
• BVOS Trial (Branch Vein Occlusion Study): Demonstrated that sectoral scatter argon laser photocoagulation applied to the non-perfused retinal quadrant halved the risk of vitreous haemorrhage (reducing haemorrhage rates from 60% down to 30%) in eyes that developed retinal neovascularisation.

Central Retinal Artery Occlusion (CRAO)

CRAO causes sudden usually painless monocular loss from inner-retinal ischaemia. A relative afferent defect, retinal whitening, segmented vessels and a cherry-red fovea support the diagnosis, but may be absent early or vary with incomplete occlusion and cilioretinal supply. The thin foveola lacks the thick inner layers that whiten elsewhere, allowing the underlying choroidal colour to remain visible. A cherry-red spot is not exclusive to CRAO.

Treat suspected acute retinal arterial occlusion as a stroke emergency. Establish symptom onset/last-known-well, activate the local emergency stroke pathway and assess vascular risk and neurological symptoms. In older patients consider giant-cell arteritis: obtain urgent inflammatory markers and treat immediately when clinically suspected, without delaying for confirmation. BRAO can preserve central acuity yet still require stroke assessment. Ocular ischaemic syndrome suggests severe carotid disease and can cause mid-peripheral haemorrhages, anterior ischaemia and delayed choroidal filling; it needs vascular evaluation as well as ocular care.

Ocular massage, anterior-chamber paracentesis and other traditional pressure manipulations have no established visual benefit and can cause harm. Animal ischaemia times are not a precise human deadline for irreversible loss.

Earlier statements about thrombolysis require the current trials. THEIA (2025) did not demonstrate a significant primary visual benefit of alteplase versus aspirin in its limited sample. TenCRAOS (2026) found no significantly better recovery with tenecteplase within 4.5 hours and reported serious safety concerns, including fatal intracranial haemorrhage. This does not support routine thrombolysis as proven ophthalmic treatment. Urgent assessment remains necessary for stroke diagnosis, prevention and any locally approved trial pathway. See THEIA and TenCRAOS.

After the acute event, address cardiovascular secondary prevention through the stroke team, monitor ocular neovascularisation in high-risk eyes and provide visual rehabilitation. Explain prognosis without promising recovery from a particular rescue manoeuvre.

Laser and Imaging Decisions

For BRVO, sector laser treats retinal or disc neovascularisation rather than nonperfusion exceeding five disc areas alone. For CRVO, conventional seven-field and ultra-widefield nonperfusion measures are not interchangeable. Monitor iris and angle before dilation when appropriate and remain vigilant after stopping anti-VEGF. Apply PRP for new vessels, with preventive treatment considered individually when reliable follow-up is impossible. Anti-VEGF primarily treats macular oedema and can suppress or delay visible new vessels without eliminating ischaemia.

SCORE: interpret the comparator before applying the result

In SCORE-CRVO, eyes with oedema from perfused CRVO received observation or preservative-free intravitreal triamcinolone 1 mg or 4 mg. Both steroid groups more often achieved the trial's 15-letter gain endpoint at 12 months; the higher dose added pressure/cataract toxicity without a demonstrated efficacy advantage. In SCORE-BRVO, the comparator was standard care, principally grid laser, and neither steroid dose demonstrated superior visual benefit at 12 months; 4 mg had more adverse effects. Read the CRVO report and BRVO report. These were different diseases and comparators. Their historical results do not establish triamcinolone as preferable to contemporary anti-VEGF treatment, nor remove the need for pressure and lens monitoring when a steroid is chosen.