Retinal vein occlusion is the second most common retinal vascular disease after diabetic retinopathy.¹ Obstruction of any of the venous vessels within the retinal vascular system results in changes in both the appearance of the fundus and the function of the retina. Blockage of a retinal vein causes elevated venous and intracapillary pressures and subsequent slowing of the arterial blood flow in the region drained by the vein. The visual defects and retinal damage from the venous obstruction depend primarily on the rapidity of its development, the severity of the occlusion, and the availability of collateral pathways of venous outflow.

Classification

Venous occlusion is divided into three anatomical categories: central retinal vein occlusion (CRVO), hemiretinal vein occlusion (HRVO), and branch retinal vein occlusion (BRVO).

Central Retinal Vein Occlusion. CRVO is a relatively common cause of loss of vision, particularly the elderly individuals, with 90% of CRVO occurring in patients 50 years of age and older.¹ CRVO develops when the circulation of the retina is compromised because of venous obstruction. CRVO is broadly divided into two main categories: ischemic and non-ischemic. The signs, symptoms, prognosis, and treatments differ between those groups.

Pathophysiology. Although the exact cause of CRVO is still unknown, both local and systemic factors appear to play a role. The central retinal vein and artery share a common sheath within the optic nerve head, and obstruction of the vein usually occurs near the narrowing at the lamina cribrosa.² Arteriosclerosis may cause crowding and narrowing of the vein, which may ultimately lead to thrombus formation and occlusion. Various stages of thrombi at this location were identified by Green et al.² Histopathology also identified inflammation at the region of the thrombus in and around the vein wall, endothelial cell proliferation, and arterial occlusive disease.² Damage to the capillary bed of the retina may lead to chronic retinal edema with permanent damage to the macular retinal cells. Ischemia of the retina may cause the release of vascular endothelial growth factor (VEGF) and other angiogenic factors that promote the development of neovascularization, particularly of the iris, with subsequent angle closure and severe glaucoma.

Risk Factors. Ocular conditions may have a predisposing effect leading to development of CRVO, including open-angle glaucoma³ and drusen of the optic nerve head.². As one might expect, systemic vascular diseases, including hypertension, cardiovascular disease, carotid artery disease, and diabetes, are also risk factors for CRVO.^3,4 Blood dyscrasias, hypercoaguable states,⁵ systemic autoimmune diseases, systemic vasculitis, and oral contraceptive use in women have been associated with CRVO.

Symptoms. Patients with CRVO present with mild to severe visual loss occurring over days to weeks. Transient obscurations of vision may precede the actual loss of central acuity. If neovascular glaucoma develops, the eye will become inflamed, edematous, and painful.

Signs. The fundus changes that occur in CRVO depend on the severity of the occlusion. In non-ischemic CRVO, there may be disc swelling, mild to moderate dilatation of the venous system in all four quadrants, flame-shaped and deep retinal hemorrhages, and a few cotton-wool spots; macular edema may or may not be present (Figure 17-1). Fluorescein angiography will demonstrate prolonged retinal circulation time, fluorescein blockage by intraretinal hemorrhages, late staining of the retinal veins, and macular edema, if present. Fewer than 10 disc areas of ischemic retina will be present. Rarely, obstruction of a cilioretinal artery may occur secondary to the increased capillary pressure within the capillary bed generated by the CRVO, and acute central visual loss will occur.⁶

Ischemic CRVO may present with an afferent pupillary defect in some patients. Fundus changes include optic disc hemorrhages and disc edema. Venous dilation is present in all quadrants along with intraretinal and deep retinal hemorrhages, multiple cotton-wool spots, and macular edema (Figures 17-2 and 17-3). A fluorescein study will show slowed retinal circulation time, blockage of fluorescein by the retinal hemorrhages and cotton-wool spots, late staining of the venous walls, macular edema, and more than 10 disc areas of capillary nonperfusion (Figure 17-4). In 15% of patients, posterior neovascularization may develop, which may cause vitreous hemorrhage.⁷ If anterior segment neovascularization occurs, iris vessels are visible both on the surface of the iris and in the angle, as seen with gonioscopy. Intraocular pressure will be elevated, often quite high; the cornea will be edematous, the conjunctiva will be inflamed and edematous, and the eyelids may be swollen.

Prognosis. The prognosis generally depends on the severity of the occlusion and the ability of the eye to compensate by developing collateral circulation. In non-ischemic CRVO, 10% of patients will retain complete recovery of vision, but 50% of patients will have 20/200 vision or less.⁸ One-third of patients who presented with non-ischemic CRVO in the Central Vein Occlusion Study (CVOS) advanced to ischemic CRVO, most within 6 to 12 months.¹ Ischemic CRVO has a much poorer prognosis, with 90% of patients having vision of 20/200 or worse and 60% developing neovascularization.¹

Management.

Workup. With an initial thrombotic event, the workup should include a physical examination and laboratory evaluation with attention to vascular disease, especially hypertension, diabetes, and hyperlipidemia. Laboratory testing may also include a lupus anticoagulant panel, anticardiolipin antibody, and homocysteine level. In patients with recurrent CRVO, a prior thrombotic episode or positive family history, testing for resistance to activated protein C, factor V Leiden gene, prothrombin gene mutation (G20210A), and other laboratory studies (e.g., anti-thrombin III, protein S, factor VIII, IX, and XI levels) may be appropriate.

Treatment. The CVOS was a multicenter, randomized, controlled trial supported by the National Eye Institute that not only studied the natural history of CRVO but also tested the effectiveness of laser photocoagulation in patients with CRVO. The use of grid laser photocoagulation for cystoid macular edema was found to be ineffective in preserving or improving central visual acuity.⁸ The study found no apparent benefit for prophylactic treatment of ischemic retina but recommended prompt panretinal laser photocoagulation in eyes in which iris and angle neovascularization develop.⁷ Because neovascular glaucoma may be prevented with laser photocoagulation, frequent (approximately monthly) follow-up examinations of patients with ischemic CRVO are recommended during the first 6 months to watch for the development of iris and angle neovascularization and glaucoma.

Several studies have suggested that anti-VEGF agents may be effective in treating both the macular edema that develops in CRVO along with the neovascularization that may form in the anterior segment.⁹

Branch Retinal Vein Occlusion. BRVO develops when one of the tributary vessels of the central retinal vein becomes obstructed. The signs, symptoms, prognosis, and treatment are all determined by the location of the occlusion in relation to the fovea, the extent of the involved injured area, and the collateral drainage capacity from the area with the compromised venous outflow to the adjacent areas of intact venous vasculature.¹⁰

Pathophysiology. BRVO occurs at the site of an arteriovenous crossing where the artery and the vein share a common adventitial sheath.¹⁰ Thickening in the artery leads to compression of the vein. Turbulent flow, endothelial damage, and ultimate compromise of the lumen of the vein ensue. Occlusion of the vein causes an upstream elevation in venous and capillary bed pressures and slowing of the arterial flow in the area drained by the vein. Retinal ischemia may lead to cellular injury and death, macular edema may cause loss of retinal function, and released angiogenic agents such as VEGF may promote growth of newly formed retinal vessels.

Risk Factors. BRVO typically occurs in middle-aged to elderly patients, and about 75% of them have systemic hypertension. Diabetes and glaucoma were not found to be risk factors. A moderate amount of alcohol consumption was found to reduce the risk of BRVO.¹¹