Retinal vein occlusion (RVO) is caused by atherosclerosis and thromboembolism, characterised by retinal haemorrhage, retinal oedema, macular ischemia, byssaceous lesions and contorted vessels. Retinal neovascularisation secondary to chronic retinal ischemia can lead to vitreous haemorrhage, retinal detachment and neovascular glaucoma. There are many differences in pathogenesis, manifestations and prognosis among patients with retinal artery and vein occlusion that must be considered when selecting the optimal therapy.
In addition, RVO depends on the anatomical location of occlusion and includes: occlusion of the central retinal vein, branches of the central retinal vein, and hemiretinal occlusion of the central retinal vein (Figure 1).
Central retinal vein occlusion (CRVO) results from a clot in the central retinal vein at the level of the lattice plate of the optic nerve, resulting in damage to the entire retina.
Central retinal vein branch occlusion (CBRVO) results in distal retinal vein branch occlusion, most often owing to compression of the superior arteriola, resulting in limited haemorrhage.
Hemiretinal central retinal vein branch occlusion results when the upper and lower retinal drains do not merge into a single central retinal vein, and one of the two trunks becomes blocked, causing damage to one half of the retina.
RVO is the second most common cause of vision loss owing to retinal vascular disease after diabetic retinopathy, with the prevalence of RVO increasing with age. CBRVO is more common than CRVO, whereas hemiretinal CBRVO is relatively rare and less well understood. The prevalence of RVO is about 2.14 cases per 1000 people over age 40 and 5.36 cases per 1000 people among patients over age 64.
- older age,
- arterial hypertension,
- diabetes mellitus (associated with CRVO but not with CBRVO),
- cardiovascular disease,
- smoking,
- obesity,
- hypercoagulation (particularly resistance to Leiden V factor and activated protein C),
- hyperlipidaemia,
- glaucoma,
- retinal arterial abnormalities.
There are ischemic and non-ischemic types of clinical RVO course, defined by the degree of capillary blockage and angiographic and the electroretinographic picture. The non-ischemic type of RVO is more common than the ischemic type and accounts for up to 65–75% of cases. In this type of RVO, the obliteration is partial, blood flow is maintained and the degree of ischemia is relatively low. At the same time, the non-ischemic type can become ischemic within 6–18 months in almost one in ten patients and, among patients older than 65, in almost one in five. In ischemic RVO, the vessel is completely blocked, blood flow is completely stopped, severe ischemia develops, and the risk of retinopathy increases.
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Symptoms characteristic of retinal vein occlusion (RVO) include scotoma or visual field deficit and blurred vision. Visual field deficit is usually associated with macular oedema and pain is uncommon. The progression of vision loss depends largely on the type and location of occlusion and on the development of macular edema:
- Central branch retinal vein occlusion (CBRVO) may be asymptomatic, but patients with macular involvement or macular oedema have complaints of central blurred vision. An area of retinal haemorrhage that is focal or wedge-shaped with a vertex located at the site of the arteriovenous junction.
- Central retinal vein occlusion (CRVO) is rarely asymptomatic: patients typically complain of sudden blurred vision. In CRVO, papilledema may occur, dilated and tortuous veins are visible, and intraretinal haemorrhages are seen in all four quadrants. About half of patients have a cotton-like lesion.
- Patients with hemiretinal CBRVO also typically complain of blurred central vision because occlusion typically affects the macula.
Iris neovascularisation, anterior chamber angle and retinal neovascularisation are common complications of CRVO and CBRVO, although they are more common in CRVO. The predictors of neovascularisation are visual acuity at diagnosis and the size of the non-perfusion area on the fluorescence angiogram. Neovascularisation develops in 35% of patients with ischemic or uncertain RVO and in 10% of patients with non-ischemic RVO.
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Therapy approaches for retinal vein occlusion (RVO) include isovolemic haemodilution, thrombolysis with a tissue plasminogen activator, surgical treatment, laser therapy and intravitreal pharmacotherapy.
Because of RVO, intravitreal injections have become first-line pharmacotherapy for symptomatic macular oedema. Data on combination therapy with intravitreal angiogenesis inhibitor (anti-VEGF) and corticosteroids are limited. Intravitreal administration of anti- VEGF is safe and effective for the treatment of macular oedema associated with central retinal vein occlusion (CRVO) and central branch retinal vein occlusion (CBRVO), with early initiation of treatment leading to better outcomes.
VEGF is a key regulator of angiogenesis and vascular permeability in the eye for both physiological and pathological processes. VEGF and interleukin-6 levels in the aqueous humour are significantly elevated in patients with CRVO, primarily in patients with retinal ischemia. Thus, they may be involved in the development and progression of macular oedema in patients with CRVO. Monthly treatment with anti-VEGF drugs lowers VEGF and interleukin-1 levels to undetectable levels and below physiological levels, but has no effect on other cytokines or growth factors. Thus, treatment with anti- VEGF drugs administered intravitreally is an option for RVO treatment.
Current recommended treatment for RVO consists of identifying and controlling cardiovascular risk factors, intravitreal administration of angiogenesis inhibitors and retinal laser therapy. Intravitreal injections have shown promising results in clinical trials.
Intravitreal use of glucocorticoids is considered to be the second line of pharmacotherapy in RVO cases. It is used to treat macular oedema, reducing inflammation and permeability of vessels. Randomised and cohort trials have shown that this approach can improve visual acuity in patients with CBRVO and CRVO. However, a systematic review of the studies found a significant loss of follow-up data and concluded that the findings of visual improvement from glucocorticoid therapy in CRVO with macular oedema should be interpreted with caution.
Used to treat complications such as retinal, iris and optic disc neovascularisation due to RVO. Panretinal laser coagulation or lattice laser coagulation is performed.
Used to reduce retinal vein compression or improve blood supply to the ischemic area. Vitrectomy pars plana and schitotomy as well as radial optic neurotomy are used. Surgical treatment is sometimes effective but associated with adverse events. In cases of surgical intervention, cataracts, vitreous haemorrhage and retinal detachment may occur, whereas laser-induced anastomosis may cause neovascularisation at the site of anastomosis, which can then be controlled by intravitreal injection of an angiogenesis inhibitor. Currently, surgical treatment is quite rare, as there are alternatives in the form of angiogenesis inhibitors, steroids and laser treatment, which are more effective and safe.
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