Central Retinal Vein Occlusion

Etiology

A primary risk factor for the development of central retinal vein occlusion is age, with 90% of patients older than 50 years old. Systemic arterial hypertension, open-angle glaucoma, diabetes mellitus, and hyperlipidemia have all been implicated as other primary risk factors for central retinal vein occlusion. Other associated risk factors include smoking, optic disc drusen, optic disc edema, hypercoagulable state (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), syphilis, sarcoidosis, African American race, sickle cell, HIV, vasculitis, drugs such as oral contraceptives or diuretics, abnormal platelet function, orbital disease, and rarely migraines.[4]

Any cause of reduced venous outflow, damage to the venous vasculature, or hypercoagulable states places the patient at an increased risk for central retinal vein occlusion. Vasculopathic risk factors can cause compression of the central retinal vein by the central retinal artery. The increased intraocular pressure in glaucoma can compromise retinal vein outflow and produces stasis. However, the exact etiology can be elusive in some cases.

Epidemiology

Central retinal vein occlusion is one of the main causes of sudden, painless vision loss in adults. The prevalence of retinal vein occlusions in the developed world has been found to be 5.20 per 1000, and the prevalence of central retinal vein occlusion is 0.8 per 1000.[5]

Pathophysiology

Three main factors contribute to thrombosis: venous stasis, endothelial damage, and hypercoagulability. Any condition that causes an increase in these factors can precipitate a central retinal vein occlusion.[6] Anatomically, the central retinal artery shares a common sheath of adventitia with the central retinal vein, located posterior to the lamina cribrosa at the arteriovenous crossing. Through the process of atherosclerosis, there may be compression of the vein by the artery. This can induce a central retinal vein occlusion.

History and Physical

Patients with CRVO will often describe the blurry or distorted vision in one eye that began suddenly. This vision loss will be painless. Neurological signs such as paresthesias, decreased extraocular movements, muscle weakness, slurred speech, ptosis, and increased deep tendon reflexes suggest a diagnosis other than central retinal vein occlusion.

Depending on the type of CRVO, the patient may have vague complaints of visual disturbance or significantly reduced vision. Similarly, they may have a relatively normal exam or exhibit an afferent pupillary defect in the affected eye, color vision reduction, and/or a reduction in visual acuity. On examination of the ocular fundus, central retinal vein occlusions are described as a “blood and thunder” appearance, which comes from the extensive hemorrhages seen throughout the retina. Other fundus findings include cotton wool spots, damage to the retinal nerve fiber layer, and swelling of the optic disc. In non-ischemic central retinal vein occlusion, an ophthalmoscopy exam typically shows tortuosity and mild dilation of the retinal veins, along with hemorrhages in all quadrants. Findings in ischemic central retinal vein occlusion typically show marked retinal edema, venous dilation, and extensive 4-quadrant hemorrhage.[7]

Evaluation

A central retinal vein occlusion requires an extensive laboratory workup to determine the cause. All patients diagnosed with a central retinal vein occlusion should get the following tests and labs:

• Blood pressure
• Erythrocyte sedimentation rate
• Complete blood count
• Random blood glucose
• Random total and HDL cholesterol
• Plasma protein electrophoresis (dysproteinemias in association with multiple myeloma)
• Urea, electrolytes, and creatinine (a renal disease in association with hypertension)
• Thyroid function tests (associated with dyslipidemia)
• EKG (left ventricular hypertrophy secondary to hypertension)

The following tests are indicated in patients either under the age of 50, with bilateral retinal vein occlusion and a history of previous thrombosis or a family history of thrombosis:[7]

• Chest x-ray (sarcoidosis, tuberculosis)
• C-reactive protein
• Thrombophilia screen (thrombin time, prothrombin time and activated partial thromboplastin time, antithrombin functional assay, protein C, protein S, activated protein C resistance, factor V Leiden mutation, prothrombin G20210A mutation; anticardiolipin antibody, lupus anticoagulant)
• Autoantibodies (rheumatoid factor, anti-nuclear antibody, anti-DNA antibody)
• Serum angiotensin-converting enzyme
• Fasting plasma homocysteine level
• Treponemal serology
• Carotid duplex imaging (exclude ocular ischemic syndrome)

Treatment / Management

No totally effective medical treatment is available for either the prevention or treatment of central retinal vein occlusion. In patients with central retinal vein occlusion, vascular endothelial growth factor (VEGF) is elevated; this leads to swelling as well as new vessels (neovascularization) that are prone to bleeding. Often treatment involves intravitreal injections of an anti-VEGF drug to reduce the new blood vessel growth and swelling. The following medical treatments have been advocated with varying success:

• Aspirin
• Anti-inflammatory agents
• Isovolemic hemodilution
• Plasmapheresis
• Systemic anticoagulation
• Fibrinolytic agents
• Systemic corticosteroids
• Intravitreal injection of alteplase
• Intravitreal injection of ranibizumab[8]
• Intravitreal injection of triamcinolone
• Intravitreal injection of bevacizumab[9]
• Intravitreal injection of aflibercept[10]
• Dexamethasone intravitreal implant
(A1)

Surgical interventions include laser photocoagulation, chorioretinal venous anastomosis, radial optic neurotomy, and vitrectomy.

There are specific surgical and laser approaches have been found to potentially improve visual acuity in patients with central retinal vein occlusion. Pars plana vitrectomy (PPV) can be done when central retinal vein occlusions have an associated vitreous hemorrhage. PPV may be used to clear the hemorrhage from the visual axis and allows for better visualization of the retina. A PPV may also ablate neovascularization that can cause neovascular glaucoma in the anterior segment. Laser pan-retinal photocoagulation (PRP) can be done to treat neovascularization, with the goal of devitalizing some of the retinal tissue to prevent further neovascularization and treat iris neovascularization. There is no evidence at this time supporting prophylactic PRP without neovascularization.[11](A1)

Differential Diagnosis

The differential diagnoses of a central retinal vein occlusion include the following:[12]

• Ocular ischemic syndrome
• Proliferative diabetic retinopathy
• Hyperviscosity retinopathy
• Branch retinal vein occlusion

Prognosis

Central retinal vein occlusion has a better prognosis in younger patients. One-third of older patients improve without treatment, one-third stay the same, and one-third get worse. If the central retinal vein occlusion does not become ischemic, return to baseline or near baseline vision occurs in about 50% of patients. Chronic macular edema is the main cause of poor vision. In most cases, the prognosis correlates with initial visual acuity.

• If visual acuity is 20/60 or better, the visual acuity is likely to remain the same.
• If the patient has 20/80-20/200 vision, the clinical course varies. Visual acuity may improve, stay the same, or worsen.
• In visual acuity worse than 20/200, improvement is unlikely.

Ischemic central retinal vein occlusion has a more variable prognosis due to macular ischemia. Patients have a high risk of neovascular glaucoma due to the development of rubeosis iris (neovascularization of the iris) in 50% of eyes, usually between 2 to 4 months. Retinal neovascularization occurs in 5% of the eyes.[3]

Complications

Central retinal vein occlusion leads to hypoxia in the retinal tissues and the subsequent release of vascular endothelial growth factor (VEGF) and inflammatory mediators. Complications of this include macular edema, vitreous hemorrhage, and neovascular glaucoma.[13]

Macular edema can lead to significant vision loss in patients with central retinal vein occlusion. Intravitreal anti-VEGF injections have been used to decrease edema and improve visual acuity.[14]

Iris neovascularization develops in two-thirds of cases of ischemic central retinal vein occlusion. When iris neovascularization develops, one-third of these develop neovascular glaucoma. A total of 10% of these cases occur in combination with branched retinal artery occlusion. The most important risk factors for iris neovascularization are poor visual acuity, large areas of retinal capillary nonperfusion, and intraretinal blood.