Introduction

Retinal vein occlusion (RVO) is a common cause of painful loss of vision, affecting an estimated 16 million people worldwide. Central retinal vein occlusion (CRVO) is around 4 times less common than branch retinal vein occlusion (BRVO) and typically results from thrombus occlusion of the central retinal vein. This mostly occurs unilaterally, although 10% of patients may subsequently develop contralateral RVO. CRVO can be further classified into ischaemic and non-ischaemic groups, delineating distinct prognoses and treatment strategies.

Epidemiology

  • Incidence: 35.00 cases per 100,000 person-years
  • Most commonly see in infants
  • Sex ratio: 1:1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Risk factors for systemic thrombosis all are important risk factors for the development of retinal vein occlusion, as well as glaucoma. Risk factors for developing ischaemic and non-ischaemic CRVO are the same.

  • Both thrombus formation in the lumen of the central retinal vein, and thrombus in the central retinal artery compressing on the adjacent retinal vein, can cause CRVO.
  • However, development of retinal vein occlusion has not been shown to be a predictor of subsequent stroke.
  • No difference in prevalence of CRVO between men and women has been demonstrated.
  • The prevalence of CRVO increases with age.
  • Disorders of coagulation and systemic auto-inflammatory conditions (e.g. (Bechet’s disease, polyarteritis nodosa, sarcoidosis) are also risk factors.
  • Rarely, retrobulbar compression of the retinal vein can cause compression e.g. from thyroid eye disease, orbital tumour or retrobulbar haemorrhage.

Pathophysiology

Visual loss in CRVO is secondary to the development of macular oedema. This develops following the venous occlusion.

  • Thrombosis in the retinal vein causes increased pressure in the vessels draining from the eye
  • This causes transudation of blood products into the retina from the venous capillary beds, leading to increased interstitial oncotic pressure that results in macular oedema and capillary ischaemia.
  • Retinal ischaemia induces vascular endothelial growth factor (VEGF) and other soluble cytokine production from retinal pigment epithelial cells.
  • These factors promote vascular permeability and neovascularization, contributing to macular oedema and further exacerbating retinal ischaemia.
  • The degree to which collateral vessels form, allowing for alternative venous drainage routes and the degree to which macular oedema has developed at presentation determines categorisation into ischaemic or non-ischaemic CRVO.
    • For example, total CRVO in a patient with well-developed collaterals may present with only mild visual acuity deficits and macular oedema.
    • Any patient with CRVO that has developed neovascularization at the angle has by definition already developed ischaemic CRVO.

Clinical features

CRVO is most often a clinical diagnosis, and assessment of risk factors alongside fundoscopy is key.

  • Symptoms:
    • Sudden, painless reduction or loss of visual acuity, usually unilaterally
    • Non-ischaemic CRVO presents with a less severe reduction in visual acuity
    • 90% of patients with ischaemic CRVO have visual acuity of 6/60 or worse

  • In the clinical history, thrombotic risk factors that may be present:
    • Smoking
    • Diabetes
    • Hypertension
    • Hyperlipidaemia
    • Hypercoagulable disorders e.g. leukaemia, myeloma, Factor V Leiden
    • Systemic inflammatory disorders e.g. Behçets disease, polyarteritis nodosa, sarcoidosis

  • Clinical examination:
    • Poor visual acuity (<6/60 on Snellen chart)
    • Relative afferent pupillary defect

  • Fundoscopy signs, to a greater degree in ischaemic CRVO versus non-ischaemic CRVO, include:
    • Optic nerve head oedema
    • Macular oedema
    • Flame-shaped haemorrhages
    • Cotton wool spots
    • Venous tortuosity

Investigations

Although largely a clinical diagnosis, blood tests can help guide ongoing risk-factor management, and imaging can determine the degree of severity.

Blood tests:
  • FBC
    • May indicate hyperviscosity, e.g. thrombocytosis
  • Lipid profile
    • Identification of modifiable risk factors
  • ESR
    • A raised ESR prompts suspicious of systemic inflammatory disorder and auto-antibody screen
  • Fasting glucose, Hba1c
    • Diabetic screen or assessment of glycaemic control

Imaging:
  • Fundus fluorescein angiography (FFA) will be done to at presentation measure areas of capillary non-perfusion. This confirms the diagnosis and can assess the severity of the condition.
    • Distinguishes between subtypes of CRVO.
    • Non-ischaemic CRVO = presence of <10 areas of non-perfusion
    • Ischaemic CRVO = presence of >=10 areas of non-perfusion
  • Optical coherence tomography (OCT)
    • Confirms extent of macular oedema
    • Can be used to monitor the response of macular oedema to treatment


Further ophthalmological clinical examination:
  • Slit-lamp examination
    • To further assess the anterior and posterior segments of the eye
    • Neovascularisation of the iris indicates severe ischaemic CRVO
  • Gonioscopy
    • To evaluate for the angle for glaucoma and neovascularisation

Differential diagnosis

There are multiple differentials for sudden painless loss of vision. If there is any accompanying peripheral or central neurological deficit, cerebral vascular accident should be ruled out.

Otherwise, the key ophthalmological differentials are:

  • Branch retinal venous occlusion
    • A less clinically severe, but far more common variant of central retinal vein occlusion
    • Differentiated by clinical examination (macular oedema is infrequently seen on fundoscopy) and imaging (fundus fluorescein angiography demonstrates only single-quadrant non-perfusion areas)
    • Treatment goals are similar, monitoring for signs of ischaemic changes warranting anti-VEGF or PRP treatment.

  • Retinal detachment
    • Sudden, painless, usually central loss of vision
    • Patients often experience floaters or photopsia, which are very unusual in CRVO
    • Area of detachment seen on fundoscopy

  • Diabetic retinopathy
    • Key risk factors present in clinical history, higher risk amongst patients with diabetes with suboptimal glycaemic control
    • Bilateral signs in diabetic retinopathy, important differentiating factor from CRVO in which unilateral symptoms are far more common
    • Fundoscopy demonstrates micro-aneurysms

  • Ischaemic optic syndrome (IOS)
    • Carotid artery stenosis leads to ocular hypoperfusion.
    • Rarer but important differential as risk of visual loss and hypoperfusion of other cerebral areas
    • Key differentiating factors on fundoscopy are microaneurysms on (common in IOS), and macular oedema (rare in IOS).

Management

Include risk factor management plus management of specific complications related to vein occlusion i.e. macular oedema and neovascularisation.

  • General measures:
    • In ischaemic and non-ischaemic CRVO, risk factor management is essential e.g. smoking cessation, diabetes control, treatment of hypertension and hyperlipidaemia.
    • Furthermore, in both categories control of glaucoma if present is essential, as anti-VEGF therapies cannot be administered with high intraocular pressures. This can be managed with ophthalmic beta-blockers, alpha-2 agonists, carbonic anhydrase inhibitors, prostaglandin analogues, or glaucoma surgery.

  • Non-ischaemic CRVO
Treatment strategy depends on the severity of presenting visual deficits.

Visual acuity
6/12 or betterCan observe with regular follow up as may spontaneously resolve. However, 30% may convert to an ischaemic CRVO over three years due to an increase in the area of non-perfusion
6/96 or betterIntravitreal anti-VEGF therapy indicated. Ranibizumab and aflibercept are two anti-VEGF agents recommended by NICE. Monthly intravitreal injections until stable visual acuity achieved.
Less than 6/96High risk of ocular neovascularisation (e.g. progression to ischaemic CRVO), and improvement with anti-VEGF therapy alone unlikely to produce improvement in visual acuity. Therefore patients should be closely observed for progression to ischaemic CRVO.

  • Ischaemic CRVO
    • Urgent pan-retinal photocoagulation (PRP) where neovascularisation is seen, with repeat at 2 weeks if required.
    • In the absence of neovascularization, monthly follow-up to monitor. Where this is impractical, prophylactic PRP may be considered.
    • Macular oedema managed with anti-VEGF therapy.