Introduction: What is CRVO?
Central retinal vein occlusion (CRVO) is the highest form of retinal vein occlusion (RVO).1 RVO is the second most common cause of vision loss from retinal vascular disease.2 CRVO occurs when the central retinal vein is occluded, or blocked, obstructing blood flow from the eye.3
The retina is a layer of tissue at the back of the eye4 that processes objects in the visual field and sends signals to your brain. A small part of the retina, called the macula, is critical for seeing fine details clearly. CRVO involves the entire retina.6
CRVO can lead to a number of complications that affect visual acuity, the sharpness or clarity of vision.7 Loss of vision in CRVO is commonly caused by a condition called macular edema, which is the accumulation of fluid in the center and most visually sensitive portion of the retina known as the macula.8 Other complications of CRVO that can lead to vision loss include vitreous hemorrhage, neovascularization and neovascular glaucoma.9
It is estimated that 16.4 million people are affected by RVO worldwide*, with 2.5 million global cases of CRVO.10 Prevalence of CRVO increases with age.11
If left untreated, people affected by CRVO can experience severe eye complications, which can cause significant vision loss. The major cause of vision loss in CRVO is swelling and thickening of the macula caused by the accumulation of fluid from leaky blood vessels, resulting in macular edema.12
*Note: This data does not account for Africa or Latin America
The retina is located between the choroid and the vitreous.
The macula is a small part of the retina. The fovea is the depressed pit in the center of the macula.13
The retina consists of multiple layers that receive blood supply from two distinct systems of blood flow (dual circulation). The outer layer of the retina receives nutrients from the choroid,14 while the inner layer of the retina receives nutrients from the central retina artery (CRA).15
The CRA runs through the optic nerve, passes through the lamina cribrosa, and enters the inner layer of the retina through the optic disc.16 The CRA branches into four branch retinal arteries either shortly before or after it passes through the lamina cribrosa, and ultimately branches into capillaries.17
The central retinal vein (CRV) drains blood from the retina. It is formed by numerous smaller vessels in the retina, the branch retinal veins,18 that come together to form the CRV.19
The CRV shares a connective tissue with the CRA20 and generally runs the same course as the CRA. The CRV exits the retina using the same path that the CRA uses to enter.21
Two types of CRVO: Non-Ischemic & Ischemic
The terminology used to describe CRVO traditionally has been inconsistent and controversial. A recent study established two types of CRVO based on the degree of capillary perfusion (blood flow in the capillaries): non-ischemic & ischemic.24 These two types differ in their progression, prognosis and treatment approaches.25
CRVO is subtyped into non-ischemic, or perfuse, if there is very limited obstruction of blood flow in the capillaries.26 Complications such as macular edema can occur in the non-ischemic (or perfuse) form.27 Up to 34% of patients with non-ischemic CRVO develop ischemia,28 so it is important that CRVO patients are regularly monitored for ischemic areas.29
CRVO is considered to be ischemic, or non perfuse, when blood flow in the retinal capillaries is more widely obstructed,30 a condition called capillary nonperfusion, causing an ischemic condition of the retina. This is a more severe form of CRVO in which vision is more likely to be poor and complications, such as neovascularization, are more likely to occur, depending on the degree of the ischemia.31 32 33 34 The degree of retinal ischemia depends on the extent of nonperfusion, so the greater the nonperfuse area, the greater the ischemia, and the greater the risk for complications.
Severity of vision loss, prognosis and response to treatment35 can be affected by the specific location and extent of the vein occlusion,36 as well as the degree of macula involvement in conditions of edema, ischemia or hemorrhage.37 Macular edema is a primary cause of vision loss in CRVO. Additional causes of vision loss in CRVO patients include traction retinal detachment, neovascular glaucoma and vitreous hemorrhage.38
The development of CRVO is not fully understood.39 The CRV generally runs the same course as the CRA and exits the retina through the same path that the CRA enters it.40 As they run their course, the CRA and CRV share a connective tissue. Occlusion typically begins when the central retinal artery compresses the central retinal vein.41 Hardening of the artery and hypertension may promote this compression.42
The compression of the CRV causes the vein to narrow and leads to increased intravascular pressure, sluggish or turbulent blood flow, endothelial cell damage43 and, ultimately, occlusion of the central retinal vein.44 The occlusion obstructs blood flow and the extent of this obstruction determines whether the CRVO is ischemic or non-ischemic.
The vein occlusion causes an upregulation (increase) in the glycoprotein vascular endothelial growth factor (VEGF),45 which weakens the vessel wall46 and increases vascular permeability.47 This results in blood vessels that leak fluid and blood into the retina, resulting in retinal and macular edema.48 Most CRVO patients have signs of swelling in the macula at diagnosis.49
CRVO is usually painless and vision loss is sudden. The condition can present with dilated or tortuous veins and intraretinal hemorrhage throughout the entire retina. Cotton-wool spots and edema of the optic disc may occur in some patients.50 Macular edema is often found in CRVO patients upon diagnosis51 and requires treatment to prevent severe or permanent vision loss. If treatment is not obtained, visual acuity continues to deteriorate in CRVO patients.52
A risk factor is anything that affects the chances of getting a disease.53 54 55 The major global risk factors for CRVO include:
The association between CRVO and other medical conditions is not yet clearly understood.56 Other factors that are commonly associated with risk for CRVO include cardiovascular disease,57 hypercoagulability,58 and end-organ damage from hypertension or diabetes.59
Symptoms & Importance of Early Diagnosis
Vision loss or distortion in vision in CRVO patients is typically sudden and painless.60 61 If you experience any changes in vision, see an eye care specialist immediately.
The later CRVO is diagnosed, the more advanced the condition is likely to be and the greater the likelihood is for visual impairment.62 The severity of visual impairment will also depend on the extent to which the retina and macula are involved.63 The risk of developing permanent structural damage to the macula increases with the duration of the edema.64
That is why it is critical to be screened for CRVO if vision loss or distortions occur, and to begin treating the condition in its early stages. The earlier the treatment is received, the better the outcomes are likely to be.65
Three common tests can detect and identify the extent of CRVO: funduscopy, fluorescein angiography and optical coherence tomography.
This test uses a hand-held ophthalmoscope to identify retinal hemorrhage or other abnormalities that indicate the presence of CRVO. A non-specialist can perform a funduscopy.66
Fluorescein angiography (FA)
If signs of CRVO are found, an eye care specialist will perform a fluorescein angiography (FA). FA is a test that takes images of the eye to evaluate the blood flow in the back of the retina.67 68 69 FA can identify the areas of capillary nonperfusion, leakage, and hemorrhage,70 which can affect treatment strategies.
When being tested with FA, the patient receives eye drops to dilate the pupil. The patient then looks into a camera that takes photos of the inside of their eye. A special vegetable dye, fluorescein, is injected into a vein in the arm71 and more pictures are taken to detect areas of obstructed blood flow or leaky vessels.72 This identifies whether hemorrhages, ischemia or macular edema have developed.73
After the test, vision may be blurred for up to 12 hours.74
Optical Coherence Tomography (OCT)
OCT is a non-invasive imaging test75 that measures the thickness of the retina and identifies the extent of edema in the retina and macula.76 77 It is a special camera that uses light to take cross section images of the inner parts of the eye.78
What You Can Do
There are steps that you can take to prevent or delay vision loss, and manage your condition and treatment:
- If you have not been diagnosed with CRVO but suspect that some of the risk factors may apply to you, go see the appropriate doctors and get tested for hypertension, vascular disorders and glaucoma. Control any modifiable risk factors that you may have.
- If you are diagnosed with CRVO, get tested for systemic risk factors, such as hypertension or diabetes. Treating systemic conditions is critical for preventing serious health complications in the future.79
- CRVO Patients should get regular check-ups to monitor progression of ischemia and edema.80 81
Understanding VEGF & CRVO
The vascular endothelial growth factor (VEGF) is a glycoprotein that has been found to contribute significantly to the development of macular edema in people with CRVO. VEGF plays an important role in many processes in the body, but excessively high levels of VEGF can have harmful effects.
VEGF significantly contributes to the development of CRVO,82 83 as well as to its complications.84, 85 Increased levels of VEGF weaken the retinal vessel wall86 and increase vascular permeability.87 When the central retinal vein is occluded, VEGF levels in the retina increase, as do its harmful effects on the retinal blood vessels. The increase in vascular permeability and weakened vessel wall cause blood vessels to leak fluid and blood into the retina, resulting in retinal edema.88 As fluid continues to accumulate in the retina, it ultimately reaches the macula and causes macular edema.
Macular edema is a common cause of vision loss in people with CRVO.89 If left untreated, vision continues to deteriorate over time, with the most severe effects in ischemic CRVO patients.90
Research has shown that over-expression of VEGF plays a significant role in the development and severity of macular edema in CRVO patients and is an important target for treating the condition.91 92