Retinal vein occlusion (RVO) is a common vascular disorder of the retina and one of the most common causes of vision loss worldwide. Specifically, it is the second most common cause of blindness from retinal vascular disease after diabetic retinopathy. RVO has been recognized as an entity since 1855, but many aspects of the pathogenesis and management of this disorder remain uncertain. In the Canadian Journal of Ophthalmology in 2007, it was noted that "Research into CRVO is fraught with challenges, from accurate disease classification to its treatment; even the most prestigious trials have become controversial."[1]
RVO is classified according to where the occlusion is located. Occlusion of the central retinal vein at the level of the optic nerve is referred to as central retinal vein occlusion (CRVO). Occlusion at the primary superior branch or primary inferior branch involving approximately half of the retina is referred to as hemiretinal vein occlusion (HRVO). Obstruction at any more distal branch of the retinal vein is referred to as branch retinal vein occlusion (BRVO). The location of the occlusion influences the pathogenesis, clinical presentation, and management of RVO.
RVO is further subdivided into nonischemic and ischemic types, according to the amount of retinal capillary ischemia seen by the ophthalmologist on fluorescein angiography. Such a distinction is relevant to the clinician, since two thirds of patients with the ischemic type develop the dreaded complications of macular edema, macular ischemia, and neovascularization that lead to blindness. However, the two subtypes cannot always be reliably distinguished based on physical examination alone and have little bearing on the initial management in the emergency department (ED). For these reasons, the emergency physician should focus on diagnosis and recognition of the clinical scenario, so that prompt management can commence and urgent ophthalmologic evaluation obtained.
RVO is essentially a blockage of a portion of the venous circulation that drains the retina. With blockage, pressure builds up in the capillaries, leading to hemorrhage and leakage of fluid and blood. This can lead to macular edema with leakage near the macula. Macular ischemia occurs when these capillaries, which supply oxygen to the retina, manifest leakage and nonperfusion. Neovascularization, new abnormal blood vessel growth, then occurs, which can result in neovascular glaucoma, vitreous hemorrhage, and, in late or severe cases, retinal detachment. Visual morbidity and blindness in RVO result from macular edema, retinal hemorrhage, macular ischemia, and neovascular glaucoma.
Intraluminal thrombus formation in RVO is associated with the venous stasis, endothelial injury, and hypercoagulability of the Virchow triad. In CRVO, the vein is typically occluded by thrombus formation consisting of fibrin and platelets at or posterior to the level of the lamina cribrosa. The inciting factor in BRVO is often compression of the adjacent vein by atherosclerotic retinal arteries at the site of AV crossing, leading to turbulent flow and venous stasis.[2, 3, 4, 5]
In both ischemic and nonischemic CRVO, blockage of the retinal vein occurs, but the nonischemic type is able to maintain better relative blood flow to the retina through collaterals. The nonischemic type of CRVO is the milder clinical presentation and accounts for 75%-80% of cases. Neovascularization is rare. Unfortunately, conversion to the ischemic type is common. The ischemic type is associated with marked decreased vision, as ischemic CRVO predisposes to anterior neovascularization called rubeosis irides, which leads to high-pressure neovascular glaucoma. Neovascularization in the posterior eye can lead to vitreous hemorrhage and retinal detachment.
Most patients with CRVO are older than 65 years. Most cases are unilateral, with approximately 6%-14% of cases bilateral. A study in Taiwan in 2008 noted a seasonal variation of CRVO, with a peak incidence occurring during the month of January.[6]
Branch retinal vein occlusion
BRVO is 3 times more common than CRVO. Men and women are affected equally, with the bulk of presentations between age 60 and 70 years.
International
A large population-based study in Israel reported a 4-year incidence of RVO of 2.14 cases per 1000 of general population older than 40 years and 5.36 cases per 1000 of general population older than 64 years.
In Australia, the prevalence of RVO ranges from 0.7% in patients aged 49-60 years to 4.6% in patients older than 80 years.
Mortality/Morbidity
The primary concern is vision loss; the morbidity of this disorder depends on the location of the occlusion and the degree of ischemia.
Neovascularization can result in neovascular glaucoma, vitreous hemorrhage, and, in late or severe cases, retinal detachment. Visual morbidity and blindness in RVO result from macular edema, retinal hemorrhage, macular ischemia, and neovascular glaucoma.
Central retinal vein occlusion/hemiretinal vein occlusion
The Central Venous Occlusion Study (CVOS) has helped to define visual loss morbidity in CRVO. Visual recovery in the study was found to vary, with the presenting visual acuity the best predictor of final visual acuity.[7] Sixty-five percent of eyes with an initial acuity of 20/40 or higher had the same or better visual acuity on final evaluation. In contrast to this, only 20% of patients who presented with an initial acuity of less than 20/200 had any significant improvement in final visual acuity. HRVO generally has an outcome similar to that of CRVO.
Patients with ischemic CRVO are much more likely to have poor visual acuity, both at initial presentation and final visual acuity, compared to those with the nonischemic type.[8]
Branch retinal vein occlusion
Patients with nonmacular BRVO may be asymptomatic, and normal visual acuity is the rule. Patients with macular involvement or edema from BRVO may have mild to (rarely) severely decreased visual acuity that may spontaneously improve within the first 3 months or so after the episode.
Race
A large 2010 study reported the prevalence of BRVO to be 2.8 per 1000 in whites, 3.5 in blacks, 5.0 in Asians, and 6.0 in Hispanics and the prevalence of CRVO to be 0.88 per 1000 in whites, 0.37 in blacks, 0.74 in Asians, and 1.0 in Hispanics.[9]
Sex
A population cohort study showed no significant difference between men and women in terms of incidence.[10]
Age
The prevalence of all types of RVO increases with age. Most CRVOs are seen in patients older than 65 years. Most BRVOs are seen in patients greater than 50 years old, with the highest rate of occurrence during the seventh and eighth decades of live. This age stratification is likely due to the association of age with atherosclerosis. When RVO is seen in younger patients, they are more likely to have an underlying coagulopathy, and patients younger than 45-50 years who lack identifiable cardiovascular risk factors should be screened for coagulopathy.
The primary concern is vision loss; the prognosis of RVO depends on the location of the occlusion and the degree of ischemia (see Mortality/Morbidity).
The history should focus on timing, severity, and character of vision loss, the presence or absence of trauma, unilateral versus bilateral, and associated symptoms. It is also important to ask about risk factors.
Branch retinal vein occlusion (BRVO) may be asymptomatic and noted incidentally on funduscopic examination, or patients may complain of relative scotoma or areas of blurred vision, classically worsening over hours to days.
Patients with central retinal vein occlusion (CRVO) are symptomatic as a rule, classically presenting with sudden painless monocular vision loss or dense central scotoma. In some cases, this loss of vision is subtle in character, with intermittent episodes of blurred vision. In other cases, it may be sudden and dramatic. The nonischemic type is often the more subtle of the two, while the ischemic type is prone to the more acute clinical presentations.
Visual acuity is the vital sign of the eye and should be documented by triage or the physician. As with any vital sign, if the documented value does not make sense, it should be rechecked by the physician personally.
Extraocular motility should be checked in every case of suspected RVO. It should be normal.
Pupillary function should be checked in every case of suspected RVO. It often appears normal during examination by a nonophthalmologist but commonly demonstrates ipsilateral relative afferent pupillary defect (RAPD) in cases of ischemic CRVO. A 2007 article in the American Journal of Ophthalmology noted that the finding of an afferent pupillary defect in ischemic CRVO is of diagnostic value.[11]
Intraocular pressure should be checked in every case of suspected RVO. IOP is generally normal in an initial acute presentation or prior to neovascularization.
Anterior slit lamp examination should be performed in every case of suspected RVO and typically yields normal findings.
Funduscopic examination is diagnostic in RVO, as it shows retinal hemorrhage, edema, and dilated veins (see image below). In patients with CRVO or hemiretinal vein occlusion (HRVO), the retinal hemorrhage is scattered and diffuse, giving the classic "blood and thunder" fundus (or hemi-fundus).
The risk factors for both BRVO and CRVO largely mirror those for vascular disease in general, including increasing age, hypertension, diabetes, smoking, obesity, and hypercoagulable disorders (such as protein C resistance-factor V Leiden, protein C and S deficiency, and antiphospholipid syndrome). Glaucoma, which causes stasis and decreased outflow, is also a significant risk factor. Increased levels of physical activity, advantageous cholesterol profiles, and alcohol consumption may be protective.
Trauma, local ocular disease, and orbital structural lesions have also been implicated in the development of RVO. Clotting can be caused by many systemic diseases, including hypercholesterolemia, hyperhomocysteinemia, systemic lupus erythematosus (SLE), sarcoidosis, tuberculosis, syphilis, multiple myeloma, cryoglobulinemia, leukemia, lymphoma, Waldenstrom macroglobulinemia, polycythemia vera, and sickle cell disease. In CRVO, a positive association has been found in ACE inhibitor use with atrial fibrillation. A negative association has been reported with the use of estrogen in postmenopausal women.
The primary concern is vision loss. Neovascularization can result in neovascular glaucoma, vitreous hemorrhage, and, in late or severe cases, retinal detachment. Visual morbidity and blindness in RVO are due to macular edema, retinal hemorrhage, macular ischemia, and neovascular glaucoma (see Mortality/Morbidity).
Extensive laboratory testing for retinal vein occlusion is not indicated. The yield from general laboratory tests for central retinal vein occlusion (CRVO) is low. Such laboratory workup may be prudent in unusual case presentations or in bilateral CRVO, in which systemic causes are more prominent etiological factors. Younger patients are more likely to have an underlying coagulopathy, and patients younger than 45-50 years who lack identifiable cardiovascular risk factors should be screened for coagulopathy by the primary doctor in consultation with the ophthalmologist.
Fluorescein angiography: The presence and severity of ischemia cannot be reliably determined at the time of physical examination in the ED. As part of the outpatient ophthalmological examination, fluorescein angiography is usually performed at the discretion of the eye specialist.
The primary directive in the ED is to make the diagnosis clinically and arrange urgent consultation with the ophthalmologist. As there is no specific ED treatment for RVO, it does not represent a true “lights and sirens” emergency. However, because of the potential for permanent vision loss, no patient should leave the ED without a sound and specific plan for urgent ophthalmological evaluation. Same-day or next-day evaluation in the office or ED is appropriate.
Of note, a systematic review of multiple small randomized trials of antithrombotic and thrombolytic medications, including aspirin, clopidogrel (Plavix), heparin, and tPA, found limited or no benefit in RVO, owing mostly to lack of available evidence.[12] Currently, there is not enough evidence to recommend the routine use of antithrombotics in RVO, except in the case of a predisposing coagulopathy.
Consultation with an ophthalmologist is necessary. All patients require a sound and specific plan for urgent ophthalmological evaluation prior to discharge. Same-day or next-day evaluation is appropriate.
The ophthalmologist’s treatment of RVO is aimed at maintaining visual acuity by monitoring the patient for and treating complications such as macular edema and neovascularization. In 2008, TheCanadian Journal of Ophthalmology noted, "No intervention has emerged as the standard of care. Current management in most centers is close observation for complications and treatment as they arise."[13]
Macular edema in patients with RVO may be treated with intravitreal anti-VEGF (first line) and/or intravitreal steroids, while neovascularization in patients with RVO (especially branched retinal vein occlusion [BRVO]) may be treated with laser photocoagulation. In refractory cases, vitrectomy may be required.
All patients diagnosed with RVO should be referred to a primary physician for routine screening for cardiovascular risk factors such as high cholesterol and diabetes. Only patients who are younger, without known risk factors for atherosclerotic RVO, or patients with a significant past medical history or family history of thrombotic events (thrombophilia, not atherosclerosis) should be referred for a hypercoagulable workup.
The primary physician’s treatment of RVO is aimed at managing predisposing risk factors. Hypertension, diabetes mellitus, atherosclerosis, and glaucoma are major risk factors in older patients. Hypercoagulability and vasculitis are key risk factors in the development of RVO in younger patients.
All patients with retinal vein occlusion (RVO) require a sound and specific plan for urgent ophthalmological evaluation prior to discharge. Same-day or next-day evaluation is appropriate.
Clinical Context:
Useful in treatment of inflammatory and autoimmune reactions. By reversing increased capillary permeability and suppressing PMN activity, it may decrease inflammation.
Clinical Context:
Corticosteroids suppress inflammation by inhibiting multiple inflammatory cytokines, resulting in decreased edema, fibrin deposition, capillary leakage, and migration of inflammatory cells. Indicated for treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.
Clinical Context:
Ranibizumab inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for the development of new blood vessels.
Jesse Borke, MD, FACEP, FAAEM, Associate Medical Director, Department of Emergency Medicine, Los Alamitos Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Audrey Xi Tai, DO, MS, Assistant Clinical Professor of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Gregory Sugalski, MD, Associate Professor, Vice-Chair of Clinical Operations, Department of Emergency Medicine, Rutgers New Jersey Medical School; Associate Chief of Service, Department of Emergency Medicine, University Hospital
Disclosure: Nothing to disclose.
Additional Contributors
Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Disclosure: Nothing to disclose.
Acknowledgements
Mark Fonrose, MD, FACEP Assistant Professor of Emergency Medicine, Kings County Hospital Center/State University of New York
Mark Fonrose, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Richard J Spitz, MD Staff Physician, Assistant Professor of Emergency Medicine, Department of Surgery, Division of Emergency Medicine, University Of Texas Health Science Center
Disclosure: Nothing to disclose.
Loice Swisher, MD Assistant Professor, Department of Emergency Medicine, Mercy Hospital of Philadelphia
Newman-Casey PA, Stem M, Talwar N, Musch DC, Besirli CG, Stein JD. Risk factors associated with developing branch retinal vein occlusion among enrollees in a United States managed care plan. Ophthalmology. Oct. 121:1939-48.
Vitreous-Retina-Macula Consultants of New York. Retinal Venous occlusive Disease: Branch Retinal Occlusion/Central Retinal Occlusion. Available at http://www.vrmny.com. Accessed: April 2008.
){kind=link}