AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Retinal vein occlusion (RVO) is a common vascular disorder of the retina and is one of the most common causes of blindness after diabetic retinopathy. RVO has been recognized as an entity since 1855 and has been noted in numerous publications. However, the pathogenesis and management of this disorder remains somewhat of an enigma. An article in the Canadian Journal of Ophthalmology 2007 noted "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 obstruction is located. Obstruction of the retinal vein at the optic nerve is referred to as central retinal vein occlusion (CRVO), and obstruction at a branch of the retinal vein is referred to as branch retinal vein occlusion (BRVO). The two forms have both differences and similarities in pathogenesis and clinical presentation. 

RVO is commonly subdivided into nonischemic and ischemic types. 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. Most investigators accept that these two entities represent varying degrees of the same underlying disease process. Yet, other clinicians and researchers argue that ischemic and nonischemic types are distinct clinical entities.

This controversy is predominantly the purview of the ophthalmology consultant. The purview of the emergency physician should center on emergency department (ED) diagnosis and recognition of the clinical scenario, so that prompt ophthalmologic evaluation and management can commence at the time of the ED visit.

Pathophysiology

Visual morbidity and blindness in retinal vein occlusion (RVO) are due to macular edema, macular ischemia, and neovascular glaucoma. The precise pathologic event in RVO is intraluminal thrombus formation, which can be associated with the abnormalities of blood flow, its constituents, and vessels consistent with the Virchow triad. CRVO has been likened to a neurovascular compartment syndrome at the site of the lamina cribrosa or closure of the final retinal vein located at the optic nerve.

The nonischemic type of CRVO is thought to be the milder clinical entity. Seventy-five to eighty percent of patients present with this form. Neovascularization is rare, at less that 2% incidence. Conversion to the ischemic type is common. However, the ischemic type is associated with marked decreased vision. This entity affects 20-25% of patients. Neovascular glaucoma is typical in the latter.

In both types, blockage of the retinal vein occurs, but the nonischemic type is able to maintain better relative blood flow to the retina through collaterals, preventing the dreaded complications known of the ischemic type. The ischemic type of CRVO predisposes to anterior neovascularization called rubeosis irides. With this, high-pressure neovascular glaucoma develops. Neovascularization in the back of the eye can lead to vitreous hemorrhage and retinal detachments.

RVO is essentially a blockage of a portion of the venous circulation that drains the retina. With blockage, a pressure build up occurs in the capillaries, leading to hemorrhages 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 is the most devastating pathologic complication with the development of abnormal blood vessel growth.

Histologically, CRVO is found to have fresh recanalized thrombus at, or just posterior to, the lamina cribrosa. The thrombi have a mild lymphocytic infiltration with prominent endothelial cells noted. Loss of retinal layers are noted and consistent with retinal ischemia. BRVO is noted for a histopathologic picture of arteriolar disease as the underlying pathology. BRVO occurs almost always at arteriovenous crossing, and it is thought that a arteriosclerotic artery compresses the retinal vein at a branch point leading to turbulent flow, endothelial damage, and vein thrombosis and obstruction.

Frequency

United States

Most patients with CRVO are male and older than 65 years. Most cases are unilateral, and approximately 6-14% of cases are found to be bilateral. A study in Taiwan in 2008 noted an interesting seasonal variation to cases.² A peak incidence was found in this greater than 20,000 patient study to occur in the month of January.

Branch retinal vein occlusion is 3 times more common than central retinal vein occlusion. 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 retinal vein occlusion 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, prevalence of vein occlusion ranges from 0.7% in patients aged 49-60 years to 4.6% in patients older than 80 years.

Mortality/Morbidity

The Central Venous Occlusion Study (CVOS) has helped to define visual loss morbidity in central retinal vein occlusion. Visual recovery in the study was found to be highly variable, and the presenting visual acuity to be the best predictor of final visual acuity.³ The natural history of the nonischemic type carries a good prognosis for a return of satisfactory visual acuity. Sixty-five percent of eyes with an initial acuity of 20/40, had the same 20/40 acuity or better on final evaluation. In about 50% of patients, vision may be 20/200 or worse, of which, 79% showed deterioration in visual acuity on follow-up.

In a third of patients with branch retinal vein occlusion, visual acuity ends up better than 20/40. However, almost two thirds of patients have evidence of some visual loss secondary to macular edema, macular ischemia, macular hemorrhage, and vitreous hemorrhage. Nonischemic CRVO may resolve completely without any complications in about 10% of cases. One third of patients may progress to the ischemic type, commonly in the first 6-12 months after presentation. In more than 90% of patients with ischemic CRVO, final visual acuity may be 20/200 or worse.

Race

Little documentation exists regarding race and RVOs; however, they are thought to be rare in the Asian and West Indian populations.

Sex

As noted above, CRVO is more commonly found in men than in women. However, BRVO has a more equal distribution in both men and women.

Age

Central retinal vein occlusion often occurs in patients older than 65 years.

In branch retinal vein occlusion, most occlusions occur after age 50 years; the highest rate of occurrence is noted in patients in their 60s and 70s.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

The evaluation of patients with unilateral visual loss should include a pertinent and thorough history of present and past medical history. Questions pertinent to the present medical history should include an inquiry into the rate of onset of visual loss, possible trauma, unilateral or bilateral in character, and if redness is present or not.

• Central retinal vein occlusion (CRVO) is essentially a diagnostic finding of painless unilateral loss of vision. 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.
• • Nonischemic CRVO - Subtle, intermittent visual loss; painless; mild-to-moderate visual loss
  • Ischemic CRVO - Acute visual loss; pain may be present;  marked visual loss
• BRVO is similar in presentation to CRVO. BRVO is often noted with an onset of blurred vision or visual field defect. Vision loss may be subtle. Patients with small occlusions of a branch retinal vein may often be asymptomatic. Larger obstructions can lead to significant visual loss. It is uniformly a unilateral disease. Nine percent of cases are bilateral.

Physical

The performance of a pertinent physical examination and mandatory evaluation for visual acuity and visual field testing is prudent. An ophthalmoscopic examination is diagnostic. An article in the American Journal of Ophthalmology 2007, notes that the finding of an afferent pupillary defect, in ischemic CRVO, is of high diagnostic precision.⁴

• Nonischemic central retinal vein occlusion
• • Mild vision loss, usually better than 20/120 measured
  • Rare afferent pupillary defect
  • Ophthalmoscopy findings consist of variable dot and flame hemorrhages in all 4 quadrants, optic nerve swelling, retinal vein engorgement and tortuosity, cotton wool spots are few
• Ischemic central retinal vein occlusion
• • Marked visual loss, usually 20/200 to only hand motion
  • Afferent pupillary defect
  • Ophthalmoscopy findings of extensive retinal hemorrhages in all 4 quadrants, optic disc is edematous, retinal vein markedly edematous and engorged
  • Macular edema is often severe.
  • Bleeding may result in vitreous hemorrhage.
  • Retinal detachment may occur.
• Branch retinal vein occlusion
• • Patients with BRVO have retinal hemorrhages confined to the distribution of the retinal vein. 
  • The ophthalmoscopic examination may note triangular and flame-shaped hemorrhages.
  • Mild obstruction of a branch may only show scant hemorrhage. Complete obstruction may have extensive hemorrhage noted on examination, with cotton wool spots.

Causes

• Local disease processes include the following: trauma, glaucoma (history of glaucoma is 5 times more likely to have CRVO), and orbital structural lesions. Rarely, is local ocular disease seen in BRVO. When it is apparent in BRVO, one can consider toxoplasmosis, Behçet syndrome, ocular sarcoidosis, and macroaneurysms.
• Systemic disease processes include the following: hypertension, atherosclerosis, diabetes, glaucoma, elderly, fasting, hypercholesterolemia, hyperhomocysteinemia, SLE, sarcoidosis, tuberculosis, syphilis, protein C resistance (factor V Leiden), protein C and S deficiency, antiphospholipid antibody disease, 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 counterintuitive finding was noted in a small study in 2007, where warfarin and aspirin use was linked with a surprising propensity to develop CRVO. A negative association can be found with the use of estrogen in postmenopausal women.
• BRVO has a strong association with hypertension.

For a related CME activity, see Hypertension and Hyperlipidemia Are Also Risk Factors for Retinal Vascular Disease.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Amaurosis fugax
Eclipse burn
Hysterical blindness (functional blindness)
Ophthalmic migraine
Retrobulbar neuritis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Extensive laboratory testing for retinal vein occlusion is usually not indicated. The yield from general laboratory tests for central retinal vein occlusion (CRVO) is so low that many authorities do not advocate these simple blood tests, as well as, extensive thrombophilia workups. Such laboratory workup may be prudent in unusual case presentations or in bilateral CRVO, where systemic causes are more prominent etiological factors.

Imaging Studies

• Fluorescein angiogram of the retinal vein is advocated by some clinicians and investigators.

Other Tests

• Focus other testing on specific ophthalmic evaluation.
• • Visual acuity is mandatory in virtually all instances.
  • Initially consider at least a gross evaluation of visual fields. Formal testing can follow at a later point.
  • Tonometry is useful.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Emergency Department Care

The cornerstone of emergency department (ED) treatment for retinal vein occlusion may rest with the awareness of the disease entity by the ED physician. When considered in the proper clinical scenario, expeditious consultation by an ophthalmologist in the ED, can enable definitive diagnosis and so that appropriate intervention and follow-up care is ensured.
 
Treatment remains controversial at the present time. The Canadian Journal of Ophthalmology 2008 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."⁵ Another 2008 study notes that many different interventions have been advocated, but evidence is lacking as to their merit. Several randomized clinical trials are underway at the present time.⁶ 

Current literature and practice for the treatment of CRVO remains controversial. Vitreous Retina Macula Consultants of New York, a large and well-established retina practice group in New York City, advocates laser photocoagulation for managing rubeosis irides.⁷ For the treatment of macular edema, they promote intraocular triamcinolone or bevacizumab (Avastin) in CRVO. Dalteparin was found superior to aspirin in improving visual acuity and preventing neovascularization in CRVO in a 2008 study.⁸ Radial optic neuropathy (RON) has shown good results in improving visual loss in severe CRVO in a limited 2008 study.⁵ Of note, a single case study in 2008 noted the use of hyperbaric oxygen, and subsequent visual improvement in a patient who refused other intervention.⁹

Current literature and practice for the treatment of BRVO is controversial as well. Vitreous Retina Macula Consultants of New York note that there is "no known medical treatment" for branch retinal vein occlusion.⁷ A small study in 2008 noted intravitreal triamcinolone and grid laser photocoagulation effective in the treatment of BRVO.¹⁰ In another 2008 study, triamcinolone acetonide retrobulbar injection was found effective for BRVO.¹¹ Pars plana vitrectomy was effective when the macular edema was resistant to improvement with triamcinolone alone.

Consultations

Ophthalmologic consultation is mandatory. Management is outside the scope of emergency medicine.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

In addition to corticosteroids, the drug bevacizumab (Avastin) is a monoclonal antibody Food and Drug Administration (FDA) approved in colon and breast cancer. Its use is experimental for macular edema in CRVO.

Drug Category: Corticosteroids

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.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Discuss decisions regarding inpatient care versus outpatient care for retinal vein occlusion with the consulting ophthalmologist.

Further Outpatient Care

• Assurance of follow-up care is extremely important if the patient is discharged from the ED.

Transfer

• Transfer may be necessary if ophthalmologic consultation is unavailable at a particular hospital.

Complications

• Decreased visual acuity
• Blindness

Prognosis

• Central retinal vein occlusion: Prognosis of visual recovery is dependent on the subtype—ischemic versus nonischemic. In general, prognosis can be predicted by visual acuity on initial examination, as noted in the Central Vein Occlusion Study (CVOS).
• Branch retinal vein occlusion: Good prognostic factors are younger age, female, and few risk factors. Poor prognosis is found in males, older patients, multiple risk factors, and those with poor initial visual acuity.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Medical and legal pitfalls can be centered upon a failure to diagnose, and subsequently offer emergent ophthalmology evaluation in the ED setting.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Richard J Spitz, MD, and Loice Swisher, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

1. Madhusudhana KC, Newsom RS. Central retinal vein occlusion: the therapeutic options. Can J Ophthalmol. Apr 2007;42(2):193-5. [Medline].
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3. D'Amico DJ, Lit ES, Viola F. Lamina puncture for central retinal vein occlusion: results of a pilot trial. Arch Ophthalmol. Jul 2006;124(7):972-7. [Medline].
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8. Farahvash MS, Moghaddam MM, Moghimi S, et al. Dalteparin in the management of recent onset central retinal vein occlusion: a comparison with acetylsalicylic acid. Can J Ophthalmol. Feb 2008;43(1):79-83. [Medline].
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10. Ozdek S, Deren YT, Gurelik G, et al. Posterior subtenon triamcinolone, intravitreal triamcinolone and grid laser photocoagulation for the treatment of macular edema in branch retinal vein occlusion. Ophthalmic Res. 2008;40(1):26-31. [Medline].
11. Kawaji T, Takano A, Inomata Y, et al. Trans-Tenon's retrobulbar triamcinolone acetonide injection for macular oedema related to branch retinal vein occlusion. Br J Ophthalmol. Jan 2008;92(1):81-3. [Medline].
12. Batioglu F, Astam N, Ozmert E. Rapid improvement of retinal and iris neovascularization after a single intravitreal bevacizumab injection in a patient with central retinal vein occlusion and neovascular glaucoma. Int Ophthalmol. Feb 2008;28(1):59-61. [Medline].
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17. Hasselbach HC, Ruefer F, Feltgen N, et al. Treatment of central retinal vein occlusion by radial optic neurotomy in 107 cases. Graefes Arch Clin Exp Ophthalmol. Aug 2007;245(8):1145-56. [Medline].
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19. Koizumi H, Ferrara DC, Brue C, et al. Central retinal vein occlusion case-control study. Am J Ophthalmol. Dec 2007;144(6):858-863. [Medline].
20. Kreutzer TC, Alge CS, Wolf AH, et al. Intravitreal bevacizumab for the treatment of macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol. Mar 2008;92(3):351-5. [Medline].
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Article Last Updated: Aug 25, 2008