Combined Central Retinal Artery and Vein Occlusion

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Article initiated by:

Katherine Han, Edward M. Nash, Rithika Sriram, Isabell Guzchenko, Sachin Pathuri, Jainam Shah, Anurag Shrivastava, MD, Bruce Becker, MD, Andrew Go Lee, MD

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Katherine Han, Edward M. Nash, Rithika Sriram, Isabell Guzchenko, Sachin Pathuri, Jainam Shah, Anurag Shrivastava, MD, Andrew Go Lee, MD, Bruce Becker, MD

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Combined central retinal artery and vein occlusion (CCRAVO) is a rare, vision-threatening retinal vascular disorder characterized by simultaneous arterial ischemia and venous obstruction, typically presenting with sudden, painless monocular vision loss. CCRAVO may be associated with systemic vascular, inflammatory, or hypercoagulable conditions and carries a substantial risk of irreversible vision loss and neovascular complications. Prompt recognition, urgent systemic evaluation, and close ophthalmic surveillance are essential to identify underlying causes and manage associated complications. This article reviews the etiology, pathophysiology, clinical presentation, diagnosis, management, and prognosis of CCRAVO.

Background

Figure 1. Color fundus photograph of the left eye of a patient with combined central retinal artery and vein occlusion (CCRAVO), demonstrating retinal whitening with a cherry-red spot and dilated, tortuous retinal vessels. Image courtesy of Hansen Dang et al., Moran Clinical Ophthalmology Resources for Education (Moran CORE), University of Utah. Available at: https://morancore.utah.edu/section-12-retina-and-vitreous/combined-retinal-vein-and-artery-occlusion-a-case-series/

Combined central retinal artery and vein occlusion (CCRAVO) is a rare, vision-threatening retinal vascular disorder involving both the central retinal artery and central retinal vein in the same eye. It typically presents with acute, painless, monocular vision loss and fundoscopic findings of arterial ischemia, such as retinal whitening, alongside signs of venous obstruction, including retinal hemorrhages and dilated, tortuous veins. Visual outcomes vary, but extensive retinal ischemia can result in severe vision loss and neovascular complications. Figure 1 illustrates a fundus image from a patient with CCRAVO.

The population incidence and prevalence of CCRAVO are not well established. In a retrospective series of 5,151 patients with retinal vascular occlusions, Raval et al. identified 17 cases (0.3%) of combined retinal arterial and venous occlusion, nine of which involved both the central retinal artery and central retinal vein. Although uncommon, CCRAVO warrants urgent ophthalmic assessment and stroke evaluation given its potential for irreversible vision loss and association with underlying vascular, inflammatory, or hypercoagulable conditions.

Etiology and Risk Factors

CCRAVO is rare, and its occurrence carries different implications from isolated arterial or venous occlusion. While isolated CRAO is most often embolic and isolated CRVO most often reflects local thrombosis from systemic vascular disease, the simultaneous occlusion of both vessels is frequently a marker of an underlying systemic disorder, including autoimmune vasculitis, a hypercoagulable state, malignancy or blood dyscrasia, and orbital or compressive pathology.

Vascular conditions: systemic vascular conditions associated with combined retinal vascular occlusion include hypertension, diabetes mellitus, dyslipidemia, and atherosclerotic disease. These conditions may contribute to endothelial dysfunction, vascular wall changes, and impaired retinal perfusion. Traditional cardiovascular risk factors are particularly relevant in older patients, although their presence does not establish the mechanism of simultaneous arterial and venous occlusion in an individual case.

Hypercoagulable and hematologic disorders: inherited and acquired thrombophilic conditions have been reported in patients with CCRAVO. These include factor V Leiden mutation, antiphospholipid syndrome, and hyperhomocysteinemia. Hyperviscosity disorders have also been implicated in combined retinal vascular occlusion, as increased blood viscosity may impair retinal blood flow and promote vascular stasis.

Inflammatory and autoimmune conditions: CCRAVO has been described in patients with systemic lupus erythematosus and Behçet disease. In these conditions, vascular inflammation and associated thrombosis may compromise both arterial and venous circulation. In systemic lupus erythematosus, combined occlusion may occur with or without detectable antiphospholipid antibodies, indicating that antiphospholipid-associated thrombosis is not the only potential mechanism. Local inflammatory conditions, including orbital inflammatory pseudotumor and posterior scleritis, have also been associated with CCRAVO. Inflammation or compression involving the optic nerve and adjacent vessels may contribute to simultaneous impairment of retinal arterial inflow and venous outflow.

Trauma and procedural associations: ocular or orbital trauma and periocular procedures, particularly retrobulbar injections, have been reported in association with CCRAVO. Proposed mechanisms include direct vascular injury, injection into the optic nerve sheath, and mechanical compression of the central retinal vessels. Combined occlusion has also been documented following cataract surgery performed under retrobulbar anesthesia.

Cases without an identifiable cause: in some patients, no underlying systemic disease, thrombophilic disorder, or local precipitating factor is identified. Such cases may be classified as idiopathic after an appropriate systemic and ocular evaluation. The absence of conventional vascular risk factors does not exclude CCRAVO or an occult associated disorder.

Pathophysiology

The central retinal artery and vein share a confined course through the optic nerve head, so a process affecting one can readily involve the other. In the original clinicopathologic series, the shared insult was localized to the retrobulbar optic nerve, where inflammation and/or cellular infiltration were implicated in simultaneous arterial and venous compromise.

The precise pathophysiology remains incompletely understood, and three mechanisms are proposed: (1) primary venous obstruction raising intraluminal and tissue pressure, reducing the arteriovenous perfusion gradient and producing secondary arterial ischemia; (2) the reverse sequence, in which primary arterial hypoperfusion causes venous stasis and secondary thrombosis; and (3) a single shared insult acting on both vessels as they traverse the optic nerve head. The combination is rare and usually signals active systemic disease, including autoimmune disorders, malignancy, blood dyscrasias, leukemia, and superior thoracic inlet lesions, and may also follow retrobulbar hemorrhage.

Experimental work supports a central role for arterial compromise in determining severity. In experimental CRVO in rhesus monkeys, venous obstruction alone produced a nonischemic, self-limited venous stasis retinopathy, whereas the severe, extensively nonperfused ischemic (hemorrhagic) picture required additional compromise of arterial perfusion, indicating that marked nonperfusion generally requires arterial as well as venous obstruction.

A related but distinct entity is CRVO with cilioretinal artery insufficiency, which appears to be reported more frequently than true combined CCRAVO. The cilioretinal artery derives its flow from the short posterior ciliary (choroidal) circulation and operates at a comparatively low perfusion pressure, owing to choroidal collaterals and the absence of retinal autoregulation. The prevailing explanation is that, after CRVO, a sharp rise in retinal capillary pressure above cilioretinal perfusion pressure impedes its flow, and the resulting ischemia manifests as paracentral acute middle maculopathy. This entity should be distinguished from true CCRAVO clinically: with a nonischemic CRVO the prognosis is generally favorable, whereas true combined occlusion carries a poor prognosis and high risk of neovascular complications, including neovascular glaucoma.

Regardless of the initiating event, the result is combined arterial ischemia and venous congestion, accounting for the coexistence of retinal whitening with intraretinal hemorrhages, venous dilation, and tortuosity, and predisposing to extensive nonperfusion and neovascular complications with poor visual outcome. No single mechanism is definitively established, and the relative contribution of arterial and venous factors likely varies between patients

Clinical Presentation and Diagnosis

Symptoms: CCRAVO typically presents with sudden, painless vision loss in one eye. The severity varies from mild visual impairment to profound vision loss.

Clinical examination: examination includes visual acuity, pupillary responses, intraocular pressure, and dilated fundus examination. A relative afferent pupillary defect may be present in the affected eye. Fundus examination shows features of both arterial and venous occlusion: retinal whitening, sometimes with a cherry-red spot, together with retinal hemorrhages, dilated and tortuous veins, and optic disc edema.

Imaging: fundus photography documents the retinal findings. Fluorescein angiography assesses delayed arterial filling, prolonged arteriovenous transit, and areas of capillary nonperfusion. Optical coherence tomography (OCT) may show inner retinal thickening and hyperreflectivity from acute ischemia, as well as associated macular edema.

Differential diagnosis: the differential diagnosis includes isolated CRAO, ischemic CRVO, CRVO with cilioretinal artery occlusion, ophthalmic artery occlusion, ocular ischemic syndrome, and occlusive retinal vasculitis. The distribution of retinal whitening, accompanying hemorrhages, and retinal and choroidal filling patterns on angiography help distinguish these conditions.

Management

Management of CCRAVO requires urgent systemic evaluation and ophthalmic treatment of ischemic complications. No established therapy reliably reverses acute retinal ischemia, and treatment is largely extrapolated from isolated CRAO and CRVO due to the rarity of combined occlusion.

Because CCRAVO involves acute retinal arterial ischemia, patients should undergo immediate evaluation through a stroke workup and a CT without contrast. Given CRAO has a high likelihood of coincident acute stroke (37.3%), assessment includes cerebrovascular and carotid imaging, cardiac evaluation, and management of cardiovascular risk factors. Giant cell arteritis should be considered in patients over 50 with suggestive clinical findings, with prompt inflammatory marker testing and empiric corticosteroids when suspicion is high. Targeted evaluation for autoimmune, inflammatory, and hypercoagulable disorders is particularly important in younger patients or those without conventional vascular risk factors.

No acute intervention has demonstrated consistent visual benefit specifically in CCRAVO. Conventional CRAO treatments, including ocular massage, anterior chamber paracentesis, and intraocular pressure-lowering agents, have not demonstrated reliable efficacy and are not routinely recommended. Intravenous thrombolysis may be considered in selected patients presenting within 4.5 hours of symptom onset, although its efficacy remains uncertain and evidence specific to CCRAVO is lacking. Decisions should be individualized through multidisciplinary stroke evaluation, particularly given the accompanying retinal hemorrhages.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy may be considered for associated macular edema, although visual improvement may be limited by irreversible retinal ischemia. Extensive retinal nonperfusion also increases the risk of iris, retinal, and angle neovascularization and subsequent neovascular glaucoma.

Panretinal photocoagulation (PRP) is generally indicated when neovascularization develops, with intravitreal anti-VEGF therapy used as an adjunct to promote rapid regression. Neovascular glaucoma may require intraocular pressure-lowering medications and, in refractory cases, glaucoma surgery.

Close ophthalmic surveillance is essential during the weeks and months following presentation, including monitoring for retinal and anterior segment neovascularization and elevated intraocular pressure. Long-term management should also address the underlying systemic etiology and cardiovascular risk factors to reduce the risk of subsequent vascular events.

Complications and Prognosis

CCRAVO carries a limited visual potential due to the combined effects of retinal arterial ischemia and venous congestion. Visual outcomes vary with the extent and duration of retinal nonperfusion, with severe cases resulting in permanent vision loss.

Extensive retinal nonperfusion promotes vascular endothelial growth factor (VEGF) production and subsequent neovascularization, including neovascular glaucoma (NVG). In a retrospective series of 17 eyes with combined retinal arterial and venous occlusions, Raval et al. reported rubeosis iridis in 46.3% and NVG in 41.2%. NVG may result in elevated intraocular pressure, ocular pain, glaucomatous optic nerve damage, and further irreversible vision loss.⁵ Because neovascularization may develop weeks to months after the initial occlusion, close ophthalmic surveillance is essential, particularly during the first six months.

Visual recovery is frequently limited by irreversible ischemic injury to the inner retina. Optical coherence tomography may demonstrate acute inner retinal thickening and hyperreflectivity followed by thinning and atrophy, while associated macular edema may further compromise central vision. In the Raval et al. series, visual acuity improved in 52.9% of eyes, remained stable in 17.7%, and worsened to perception of light in 29.4%. These outcomes reflect a mixed cohort of central and branch retinal vascular occlusions rather than isolated CCRAVO.