Laboratory Studies
No laboratory studies are routinely indicated in the diagnosis of central retinal vein occlusion (CRVO). In older patients, laboratory testing should be directed toward identifying systemic vascular problems. In young patients, laboratory testing may be tailored depending upon individual findings, to include the following:
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Complete blood cell (CBC) count
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Glucose tolerance test
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Lipid profile
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Serum protein electrophoresis
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Chemistry profile
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Hematologic tests
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Syphilis serology
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In addition, thrombophilic screening, activated protein C resistance, lupus anticoagulant, anticardiolipin antibodies, protein C, protein S, and antithrombin III may be completed.
Imaging Studies
Color Doppler imaging is a noninvasive quantitative method of assessing the retrobulbar circulation. Detection of low venous velocities has been used to predict the onset of iris neovascularization. At present, this is performed as an investigational procedure in large facilities. [19]
Optical coherence tomography (OCT) [20] scanning is a noninvasive, noncontact, transpupillary imaging technology that can image retinal structures in vivo with an axial resolution of 1-15 µm. Spectral-domain OCT is used to detect intraretinal and subretinal fluid and to measure the thickness of individual retinal layers. OCT provides information regarding the health of photoreceptors and ganglion cell layers. OCT is used exclusively to monitor macular edema over time and the response with various treatment modalities. [20, 21]
In addition to providing quantitative measurements of central retinal thickness, spectral-domain OCT reveals disorganization of the retinal inner layers (DRIL) and ellipsoid zone disruptions, which are used increasingly as biomarkers for assessing visual outcomes to various therapeutic agents. [22]
Other Tests
Fluorescein angiography
Fluorescein angiography is the most useful test for the evaluation of retinal capillary nonperfusion, posterior segment neovascularization, and macular edema. [2] Note the images below.
Fluorescein angiogram of a patient with nonischemic central retinal vein occlusion, showing staining of dilated tortuous veins with leakage into macula in a cystoid pattern.
Fluorescein angiogram of the same patient as in previous image, showing perifoveal capillary leakage in a cystoid pattern in late phases of angiogram.
Late phase of fluorescein angiograph of the same patient as in previous image, showing cystoid pattern of leakage from perifoveal dilated leaking capillary network.
Fluorescein angiography is one of the tests used in the classification of CRVO. Areas of capillary nonperfusion are visualized as hypofluorescence, but hemorrhages can block fluorescence and give a similar picture. Therefore, in the early stages of the disease process, due to extensive hemorrhages, fluorescein angiography gives little information regarding the perfusion status of the retina. Once the hemorrhages clear, areas of capillary nonperfusion can be detected as hypofluorescence in the fluorescein angiography. Wide-angled fluorescein angiography is useful tool to detect areas of retinal perfusion and non-perfusion in mid and peripheral retina in early stages of disease. [23]
Various studies have reported different criteria for defining ischemic CRVO versus nonischemic CRVO based on the extent of capillary nonperfusion of the retina. The amount of retinal nonperfusion ranges from 10-30 disc areas.
In addition, fluorescein angiography may show delayed arteriovenous transit, staining along the retinal veins, microaneurysms, arteriovenous collaterals, NVD, NVE, and dilated optic nerve head capillaries.
In a nonischemic central retinal vein obstruction, angiography may show minimal or absent retinal capillary nonperfusion, staining along the retinal veins, microaneurysms, and dilated optic nerve head capillaries. Resolved CRVO may be completely normal.
Macular edema may be detected as leakage from perifoveal capillaries (depicted in the image below), leakage from microaneurysms, or diffuse leakage on fluorescein angiography. If extensive edema is present, fluorescein angiography may show pooling of dye in large cystoid spaces. In addition, capillary nonperfusion around the fovea may indicate macular ischemia. If macular edema persists, pigmentary changes become evident.
Arteriovenous phase of fluorescein angiograph showing perifoveal capillary leakage in a patient with nonischemic central retinal vein occlusion.
Optical coherence tomography angiography
OCT angiography (OCTA) generates high-resolution noninvasive angiograms (no dye injection required) that qualitatively illustrate most clinically relevant findings in retinal venous occlusion. Unlike standard fluorescein angiography, OCTA provides details of superficial and deep retinal capillary plexus and choroidal capillary structures, which are affected by retinal vein occlusions. OCT angiography is a useful tool in evaluating capillary nonperfusion, which can allow for more objective differentiation of ischemic CRVO from nonischemic CRVO. [23, 24, 25]
OCT angiography provides great details about the superficial and deep capillary plexus in patients with CRVO associated with macular edema. Capillary network abnormalities including capillary network disruption or dilation were observed in both the superficial and deep capillary plexus in patients with CRVO. [26]
Electroretinography
Electroretinography (ERG) is another useful test to evaluate the functional status of the retina and to classify CRVO. [20, 27, 28] In ERG waveform, b-wave and a-wave are produced by the inner retina and the outer retina, respectively. In central retinal vein obstruction, perfusion of the inner retina is affected, so that the amplitude of the b-wave is decreased relative to the a-wave; the b-to-a ratio has been shown to be reduced. Some studies indicate that a b-to-a ratio of less than 1 suggests an ischemic central retinal vein obstruction.
Histologic Findings
Not many histopathologic reports exist in the literature. A report of histologic sections of 29 eyes with central retinal vein obstruction showed a fresh or recanalized thrombus at or just posterior to the lamina cribrosa. Within the thrombi, a mild lymphocytic infiltration with prominent endothelial cells was seen. Loss of the inner retinal layers consistent with inner retinal ischemia also was seen. [29]
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Recent onset central retinal vein occlusion, showing extensive hemorrhages in the posterior pole and giving the "blood and thunder appearance."
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Peripheral fundus view of the same patient with central retinal vein occlusion as in the previous image, showing hemorrhages extending all over the fundus.
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Fluorescein angiograph of same patient with central retinal vein occlusion as in previous images, showing hypofluorescence due to blockage from hemorrhages in the retina. It is not useful to perform a fluorescein angiogram in acute stages of the disease.
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Fundus picture of the same patient with central retinal vein occlusion as in previous images, showing resolving neovascularization of the disc and panretinal photocoagulation scars.
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Fluorescein angiogram of the same patient with central retinal vein occlusion as in the previous images, taken more than 1 year later, showing persistent cystoid macular edema with good laser spots.
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Patient with nonischemic central retinal vein occlusion presented with dilated, tortuous veins and superficial hemorrhages.
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Fundus picture of the same patient with central retinal vein occlusion as in previous image, showing resolved hemorrhages and pigmentary changes in the macula several months later.
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Central retinal vein occlusion showing significant disc edema with dilated tortuous veins and scattered retinal hemorrhages.
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Fluorescein angiogram of the same patient with central retinal vein occlusion in as in previous image, showing leakage from disc, staining of retinal veins.
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Fundus of a patient with nonischemic central retinal vein occlusion, showing few scattered peripheral fundus hemorrhages.
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Scattered retinal hemorrhages in a patient with central retinal vein occlusion.
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Fluorescein angiogram of a patient with nonischemic central retinal vein occlusion, showing staining of dilated tortuous veins with leakage into macula in a cystoid pattern.
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Fluorescein angiogram of the same patient as in previous image, showing perifoveal capillary leakage in a cystoid pattern in late phases of angiogram.
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Late phase of fluorescein angiograph of the same patient as in previous image, showing cystoid pattern of leakage from perifoveal dilated leaking capillary network.
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Arteriovenous phase of fluorescein angiograph showing perifoveal capillary leakage in a patient with nonischemic central retinal vein occlusion.
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Fundus picture of a well-compensated, old central retinal vein occlusion showing optociliary shunt vessels.
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Red-free photo of the same patient with central retinal vein occlusion as in the previous image, showing prominent optociliary shunt vessels.
