Definition

The term retinal vein occlusion (RVO) indicates a heterogeneous group of vascular retinal disorders that can seriously degrade vision; these disorders have different pathogeneses, clinical aspects, progresses, and complications.
Retinal vein occlusions occur when circulation in a retinal vein is hindered:  the occlusion leads to the formation of retinal haemorrhage and commonly causes the development of ischemic areas (areas with limited blood circulation) and/or macular edema. Occlusions that affect the central retinal vein are known as central retinal vein occlusions (CRVO), while those that affect a branch thereof are known as branch retinal vein occlusions (BRVO). Central retinal vein occlusions occur mainly in the lamina cribrosa, and occlusions are caused by turbulent blood flow and the attendant presence of other rheological factors or pariteal alterations.
Branch retinal vein occlusions instead mostly occur at an arteriovenous intersection, and it seems that these occlusions are caused by a combination of factors including mechanical obstruction and higher blood viscosity.

Epidemiological notes

Worldwide, RVO, standardized by age and sex, affects 5.2 people out of every 1,000 (BRVO 4.42 and CRVO 0.80); it affects men and women similarly and its frequency increases with age.

Risk factors

There are numerous risk factors for RVO, and they are generally the same as for vascular alterations involving other parts of the body, such as stroke or coronary disease. For both central retinal vein occlusion and branch retinal vein occlusion, the main risk factors are cardiovascular ones, such as atherosclerosis, high blood pressure, diabetes mellitus, hyperlipidemia, obesity, smoking, and carotid occlusion. Other significant risk factors include rheological alterations (high hematocrit, high plasma viscosity, high red blood cell aggregation, reduced red blood cell deformability). Indeed, the capillaries of the retinal periphera are of a lower calibre than the size of hematocrit, and only very elastic hematocrit that can shift shape can go through them. Additionally, changes in plasma viscosity are extremely important: patients affected by hyperviscosity syndrome can show bilateral central retinal vein occlusion. Other significant risk factors regard thrombophilic states: hyperhomocysteinemia, antiphospholipid antibodies, activated protein C resistance (factor V Leiden), mutations, reduced levels of  plasminogen inhibitors, and oral contraceptives.
There are also important local risk factors: glaucoma (risk of CRVO 5-7 higher than in healthy individuals); trauma (generally present in the anamnesis of CRVO patients); retinal vasculitis; occlusion of the central artery; all the conditions that cause a narrowing of the lamina cribrosa canal, such as drusen, papilledema; arteriovenous malformations causing venous hypertension; hyperviscosity syndrome (polycythemia, macroglobulinemia, myeloma, leukemia).

Diagnosis

Today, retinal vein occlusion is still  principally diagnosed through an ophthalmoscopic evaluation; nevertheless, morphological and functional tests are extremely useful. Recent literature suggests earlier diagnosis and treatment and commonly performed diagnostic tests are: ophthalmoscopy, biomicroscopic examination of the ocular background, fluorangiography and OCT (especially useful in patient follow-up). In young RVO patients aged 43 to 69 years, the increased risk of cardiovascular mortality requires primary prophylaxis of cardiovascular events by long-term treatment with antithrombotic drugs.

Therapy

Intravitreal therapies

The use of anti-VEGF drugs in vascular retinal disorders leads to an improvement of visual acuity and a reduction of macular thickness, in the short term, requires a number of multiple injections for the management of the pathology (repeating the procedure). Currently, the anti-VEGF drugs reimbursed by the national health system in the treatment of post-occlusive macular edema are Ranibizumab and Aflibercept.

With regard to the need to resort to a number of multiple intravitreal injections, with the relative managerial and economic difficulties, the approval by the FDA, the EMA and the subsequent reimbursement by the National Health System of the intravitreal slow release implant of Desametasone (Ozurdex®) has provided an important aid in the treatment of these diseases. This device has, in fact, a more long-lasting effectiveness in reducing diabetic macular oedema while maintaining a high safety profile.

Laser therapy

Laser therapy is not a suitable treatment for RVO;  it can be used exclusively for treating complications from RVO (macular edema or neovascularisation). Laser therapy has long been the standard of care for secondary macular edema caused by branch retinal vein occlusion; in case of ischemic CRVO or secondary retinal neovascularisation due to OBVCR peripheral laser treatment is useful for controlling neoangiogenesis. The surgical approach is not justified by strong evidence; however, there are some particular clinical situations in which evidence of vitreal co-participation may justify the surgical approach.