Nixon Phua Cher Yang
Foundation Trainee at Imperial College NHS Healthcare Trust
Introduction
Retinal vein occlusion is a common retinal vascular disease and cause of visual loss. Depending on the location of obstruction, it can be classified into central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO) and hemi-retinal vein occlusion (HRVO). The condition is labelled as CRVO if the blockage of central retinal vein takes place at the lamina cribrosa. Based on the area of capillary non-perfusion, CRVO can be sub-divided into ischaemic and non-ischaemic types. Ischaemic CRVO is defined by the Central Retinal Vein Occlusion Study (CVOS) as CRVO with fluorescein angiographic evidence of >10 disc areas of capillary nonperfusion on seven-field fundus fluorescein angiography (1).
Epidemiology
Retinal vein occlusion is the second commonest retinal vascular disorder after diabetic retinopathy. The global prevalence of CRVO is 0.13%, equivalent to an overall 4.67 million affected people based on a meta-analysis performed in 2015 (2). The prevalence of RVO also increases with age. German data demonstrates that prevalence of RVO was 0.2% in participants aged under 55years, 0.48% in those aged 55-64 years, and 0.92% in those aged 65-74 years (3).
Pathophysiology and risk factors
CRVO is linked to thrombosis of central retinal vein. From an anatomical perspective, thrombosis is likely secondary to venous compression at the lamina cribrosa caused by atherosclerosis of adjacent central retinal artery because central retinal artery shares a common sheath of adventitia with the central retinal vein. Thrombosis can also be caused by venous stasis and hypercoagulability. In rare instances, CRVO can also happen as a result of retro-bulbar external compression from orbital tumour, thyroid eye disease or retrobulbar haemorrhage (4). Main risk factors of CRVO are those associated with atherosclerosis such as hypertension, diabetes mellitus and hyperlipidaemia. The Eye Disease Case-Control Study Group showed that risk of CRVO is higher in people with hypertension and glaucoma. The risk is also found to be lower in people with high level of physical activity and low level of alcohol consumption (5). Risk factors linked to hypercoagulability include polycythemia, multiple myeloma, cryoglobulinemia, Waldenstrom macroglobulinemia, antiphospholipid syndrome, Leiden factor V, activated protein C resistance, hyperhomocysteinemia, Protein C and S deficiency, antithrombin III mutation, prothrombin mutation (6).
Clinical presentation
Patients typically present with sudden-onset, unilateral blurred vision. The visual loss if often painless. Compared to non-ischaemic CRVO, CRVO is associated with poorer visual acuity (often <6/60) and more marked relative afferent pupillary defect. Fundoscopy often shows “stormy sunset appearance”, which is characterised by flame haemorrhages, cotton wool spots and retinal vein tortuosity. Ischaemic CRVO fundoscopic findings usually comprise of marked retinal oedema, multiple haemorrhages and extensive venous dilation in all quadrants. On the other hand, in non-ischaemic CRVO, only mild retinal tortuosity and haemorrhage are found.
Assessment and investigations
Royal College of Ophthalmologists (RCOphth) recommends checking blood pressure, serum glucose, full blood count (FBC) erythrocyte sedimentation rate (ESR) for every patient suspected of RVO (4). The rationale is to help identify associations with RVO that warrant urgent intervention such as malignant hypertension, poorly controlled diabetes with end-organ damage and haematological condition such as leukemia or myeloma.
Routine thrombophilia testing with patients diagnosed with RVO is not currently recommended by the British Society of Haematologist (7).
Fluorescein angiography is conducted to differentiate ischaemic CRVO from non-ischaemic CRVO. In ischaemic CRVO, the retinal capillary non-perfusion will be more than 10 disc-areas. Besides that, optical coherence tomography is performed to assessed macular oedema. OCT of CRVO typically demonstrates cystoid macular oedema. Subfoveal fluid and epiretinal membrane can sometimes be seen on OCT as well. Tonometry should be carried out to measure intraocular pressure. Goniscopy should be performed, especially if ischaemic CRVO is suspected.
Management
Vascular endothelial growth factor (VEGF) is often raised in CRVO. Raised VEGF could lead to neovascularisation, whereby there is a rapid development of new vessels that easily bleed. Anti-VEGF could be given to slow down the vessel growth. In terms of surgical interventions, pan-retinal photocoagulation (PRP) is typically offered to achieve similar aim.
Management of CRVO depends on whether it is ischaemic or non-ischaemic in nature based on guidance written by RCOphth. In non-ischaemic CRVO, intravitreal anti-VEGF is offered if the visual acuity is 6/96 or better and if macular oedema is noted on OCT. NICE currently recommend two anti-VEGF agents, namely Ranibizumab and aflibercept. In ischaemic CRVO, if iris or angle neovascularisation is noted and if anterior chamber angle is open, urgent PRP should be offered. However, if the anterior chamber is closed with concurrently raised intraocular pressure, urgent PRP with cyclodiode-laser therapy or tube-shunt operation should be offered instead (4).
Conclusion
CRVO is a common cause of visual loss, especially among the elderly population. Careful assessment is essential for the early detection of associating conditions. It is also important to be able to differentiate ischaemic CRVO from non-ischaemic CRVO because they are managed differently and carry different prognoses.
References
1. Harkins T. The central vein occlusion study. Clinical Eye and Vision Care. 1996 Jun 1;8(2):123-6.
2. Song P, Xu Y, Zha M, Zhang Y, Rudan I. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors. Journal of global health. 2019 Jun;9(1).
3. Ponto KA, Elbaz H, Peto T, Laubert‐Reh D, Binder H, Wild PS, Lackner K, Pfeiffer N, Mirshahi A. Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study. Journal of Thrombosis and Haemostasis. 2015 Jul;13(7):1254-63.
4. Sivaprasad S, Amoaku WM, Hykin PR. The Royal College of Ophthalmologists Guidelines on retinal vein occlusions: executive summary. Eye. 2015 Dec;29(12):1633-8.
5. Sperduto S. Risk factors for central retinal vein occlusion the eye disease case-control study group. Archives of Ophthalmology. 1996;114(5):545-54.
6. Blair K, Czyz CN. Central retinal vein occlusion.
7. Tait RC, Baglin T, Watson H, Laffan M, Makris M, Perry D, Keeling D. Guidelines on the investigation and management of venous thrombosis at unusual sites. British journal of haematology. 2012;159(1):28-38.