Central Retinal Vein Occlusion
In CRVO, vision loss is most commonly sudden, with severity ranging along a continuum from mild (nonischemic) to severe (ischemic). Less commonly, patients may experience premonitory symptoms of transient obscuration of vision before overt retinal manifestations appear. CRVOs are considered intermediate, or indeterminate, if they are neither clearly ischemic nor nonischemic; however, more than 80% of intermediate eyes progressed to ischemic disease in the Central Vein Occlusion Study (CVOS).
Nonischemic (mild) CRVO, sometimes referred to as partial, perfused, or venous stasis retinopathy, is characterized by visual acuity of 20/200 or better, mild or no afferent pupillary defect, and mild visual field changes. Ophthalmoscopy shows mild dilation and tortuosity of all branches of the central retinal vein as well as dot- and flame-shaped hemorrhages in all quadrants of the retina (Fig 6-9). Macular edema with decreased visual acuity and mild optic nerve head swelling may be present (Activity 6-1; Fig 6-10). Fluorescein angiography usually demonstrates prolongation of the retinal circulation time with breakdown of capillary permeability but minimal areas of nonperfusion. Anterior segment neovascularization is rare in mild CRVO. Chronic nonischemic changes from CRVO include telangiectasias, microaneurysms, and macular pigmentary changes (see Fig 6-6).
OCT Activity: Macular OCT of CRVO eye with severe CME and foveal detachment.
Courtesy of Colin A. McCannel, MD.
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Ischemic (severe) CRVO, also known as complete, nonperfused, or hemorrhagic retinopathy, is defined as having at least 10 optic disc areas of retinal capillary nonperfusion on fluorescein angiography. Ischemic cases are usually associated with poor vision, an afferent pupillary defect, dense central scotoma, and peripheral field constriction. Marked venous dilation, more extensive 4-quadrant hemorrhage, retinal edema (Fig 6-11), and variable numbers of cotton-wool spots are frequently found as well. Fluorescein angiography circulation times are typically prolonged and widespread capillary nonperfusion is demonstrated. Because of inner retinal dysfunction due to ischemia, the b- to a-wave amplitude ratio is decreased in electroretinographic bright-flash, dark-adapted testing. The CVOS showed that visual prognosis is generally poor, with only approximately 10% of eyes achieving vision better than 20/400. With anti-VEGF treatment, the prognosis may be somewhat better in all but the most ischemic cases.
Hemiretinal vein occlusion (HRVO), which shares features with both CRVO and BRVO, has been associated with a congenital variation in central vein anatomy; it may involve either the superior or inferior half of the retina (Fig 6-12).
Figure 6-9 Moderate to severe nonischemic CRVO. A, Ultra-wide-field fundus photograph of moderate to severe nonischemic, or perfused, CRVO in an eye with 20/80 visual acuity. Dilated retinal veins and retinal hemorrhages are present in all 4 quadrants. Cotton-wool spots can be seen near the optic nerve head. B, A fluorescein angiography image taken at 1 minute, 8 seconds reveals relatively intact perfusion of the retinal capillary bed but dilated vessels and peripheral leakage from the large vessels. There are some areas of capillary nonperfusion in the superior macula. C, An SD-OCT scan shows severe cystoid retinal edema with a serous foveal detachment. After 2.5 years of anti–vascular endothelial growth factor (VEGF) treatment with bevacizumab, the patient maintains a visual acuity of 20/40.
(Courtesy of Colin A. McCannel, MD.)
Figure 6-10 Macular OCT of eye shown in Figure 6-9 demonstrates severe CME with foveal detachment. There is also mild to moderate inner retinal hyperreflectivity, consistent with some degree of ischemia. However, the fluorescein images of the retina (Fig 6-9) show that perfusion is present.
(Courtesy of Colin A. McCannel, MD.)
Figure 6-11 Ischemic CRVO. A, Ultra-wide-field fundus photograph of severe, or ischemic, CRVO in an eye with hand motions visual acuity. The veins are dilated, and extensive retinal hemorrhages are present. B, Ultra-wide-field fluorescein angiography image corresponding to A taken 40 seconds after injection reveals widespread retinal capillary nonperfusion, which causes the midsize and larger retinal vessels to stand out from the gray-black, nonperfused areas.
(Courtesy of Colin A. McCannel, MD.)
Figure 6-12 Hemiretinal vein occlusion. A, Fundus photograph shows superior involvement with intraretinal hemorrhage. B, Fluorescein angiography image shows blockage of underlying details in areas of hemorrhage. Note that the foveal avascular zone is largely intact.
Histologic studies suggest that most forms of CRVO share a common mechanism: thrombosis of the central retinal vein at or posterior to the level of the lamina cribrosa. It is postulated that, in some cases, a thickened central retinal artery may impinge on the central retinal vein, causing turbulence, endothelial damage, and thrombus formation. When thrombosis is more anterior, fewer collaterals are available, resulting in greater ischemia.
Iris neovascularization in CRVO
Among eyes with severely ischemic CRVO, the incidence of anterior segment neovascularization, iris and angle, is high (up to 60%); this development occurs on average 3–5 months after the onset of symptoms. If not detected promptly, neovascular glaucoma may develop. The CVOS found that poor visual acuity is the risk factor most predictive of iris neovascularization in central venous occlusive disease. Other risk factors include large areas of retinal capillary nonperfusion and intraretinal blood.
Baseline and early natural history report. The Central Vein Occlusion Study. Arch Ophthalmol. 1993;111(8):1087–1095.
Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. 2008;126(4):513–518.
Risk factors and causes of CRVO
The most important risk factor for the development of CRVO is age; 90% of patients are older than 50 years at the time of onset. Mild CRVOs generally occur at a younger age. The Eye Disease Case-Control Study and other studies found the following additional risk factors associated with CRVO:
It is common for patients presenting with CRVO to have elevated intraocular pressure (IOP) or frank open-angle glaucoma, either only in the affected eye or in both eyes; if CRVO is present in 1 eye, it is important to assess the fellow eye for glaucoma. CRVO can also lead to a transient shallowing of the anterior chamber that, in some instances, leads to angle-closure glaucoma.
Oral contraceptives and diuretics have been implicated as risk factors for the development of CRVO. Although rare, predisposing hypercoagulable conditions may be present; these abnormalities include hyperhomocysteinemia, protein S deficiency, protein C deficiency, and disorders associated with vasculitis such as sarcoidosis and systemic lupus erythematosus. However, when CRVO occurs in patients older than 50 years, it is generally considered unnecessary to pursue an elaborate systemic workup.
Differential diagnosis of CRVO
It is particularly important to recognize that hyperviscosity retinopathy can mimic a typical CRVO. However, the retinal findings in hyperviscosity retinopathy are generally bilateral and are usually related to dysproteinemia, for example, that associated with Waldenström macroglobulinemia, multiple myeloma, or blood dyscrasias (eg, polycythemia vera). In many cases, the hyperviscosity can be reversed by treating the underlying condition. To assess for these conditions, diagnostic testing may include complete blood count, serum protein electrophoresis, and a measure of whole-blood viscosity. Ocular ischemic syndrome can also mimic CRVO, but hemorrhages are limited to the deeper retinal layers and vascular tortuosity is absent. Unusual diseases that affect the blood vessel wall, blood-clotting mechanisms, or blood viscosity may also produce a CRVO-like picture.
Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol. 1997;115(4):486–491.
Fuller JJ, Mason JO III. Retinal vein occlusions: update on diagnostic and therapeutic advances. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2007, module 5.
Evaluation and management of CRVO
To determine whether the vein occlusion is nonischemic or ischemic, the examiner should assess the patient’s visual acuity, visual fields, and relative afferent defect via ophthalmoscopy, fluorescein angiography, OCT, and electroretinography. It is important to perform gonioscopy regularly during follow-up to check for angle neovascularization.
If the evaluation indicates that common risk factors for CRVO are absent, or if the patient is less than 50 years of age, a thorough investigation should be considered, possibly including a workup for thrombophilia.
Patients with CRVO should be warned about the possibility of worsening vision; eyes that initially appear perfused sometimes develop progressive ischemia. During the CVOS, 16% of initially nonischemic CRVOs converted to ischemia by 4 months of follow-up; by 36 months, the percentage had increased to 34%.
Follow-up In the absence of treatment, patients with CRVO should be monitored monthly during the first 6 months for evidence of progression and development of anterior segment neovascularization or neovascular glaucoma. Patients treated with anti-VEGF agents should be observed for a similar duration after discontinuation of the drugs.
Complications The most common complications of CRVO are vitreous hemorrhage, anterior segment neovascularization, and neovascular glaucoma. Vitreous hemorrhage may occur in the absence of obvious neovascularization, and neovascular glaucoma can occur from angle neovascularization with or without iris neovascularization.
Stem MS, Talwar N, Comer GM, Stein JD. A longitudinal analysis of risk factors associated with central retinal vein occlusion. Ophthalmology. 2013;120(2):362–370.
Treatment of CRVO
Pharmacologic management Pharmacologic management is currently the mainstay of RVO management. See the section Pharmacologic Management of Retinal Vein Occlusion for a discussion of this topic.
Surgical management of CRVO
MACULAR LASER SURGERY
The CVOS demonstrated that grid pattern laser in CRVO with macular edema does not improve visual acuity and is therefore not recommended.
The CVOS found that prophylactic panretinal photocoagulation (PRP) did not result in a statistically significant decrease in the incidence of iris neovascularization. In fact, 20% of participants who received the prophylactic PRP still developed iris neovascularization. Therefore, patients at high risk of iris neovascularization should be closely monitored. Although the CVOS investigators recommended waiting until an undilated gonioscopic examination revealed at least 2 clock-hours of iris neovascularization before performing PRP, in clinical practice PRP is often performed at the first sign of iris neovascularization, particularly when close follow-up is not possible or seems unlikely. Wide-field angiography provides expanded visualization of peripheral nonperfusion in CRVO; however, there is no evidence to support altered treatment criteria based on this information.
PARS PLANA VITRECTOMY
CRVOs complicated by vitreous hemorrhage may benefit from pars plana vitrectomy. Vitrectomy is used for vision rehabilitation or to accomplish retinal ablative treatment in the management of anterior segment neovascularization and neovascular glaucoma. For neovascular glaucoma, a glaucoma valve may be implanted concurrently.
OTHER SURGICAL APPROACHES
Several surgical approaches have been abandoned due to lack of evidence for their efficacy and/or their high complication rates. These approaches include creation of peripheral laser anastomosis between a retinal vein and the choroidal circulation, radial relaxing incision of the optic nerve scleral ring to decompress the central retinal vein, and retinal vein cannulation with infusion of tissue plasminogen activator (tPA).
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.