Retinal Vein Occlusion

Key Points at a Glance

Highlights of This Disease

• Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy.
• It is broadly classified into branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), with prevalence rates of approximately 2.0% for BRVO and 0.2% for CRVO.
• Main symptoms include sudden vision loss and visual field defects in one eye, with macular edema being the primary cause of vision loss.
• Hypertension, arteriosclerosis, and diabetes are major risk factors, and management of systemic diseases is important.
• Intravitreal injection of anti-VEGF agents is the first-line treatment for macular edema.
• In central retinal vein occlusion, about 25% of cases develop iris neovascularization, which can lead to neovascular glaucoma.

1. What is Retinal Vein Occlusion?

Retinal vein occlusion (RVO) is a disease in which retinal blood flow is impaired due to occlusion of a retinal vein. It is known as the second most common retinal vascular disease after diabetic retinopathy¹⁾.

Based on the occlusion site, it is classified into the following three types¹⁾:

Branch Retinal Vein Occlusion (Branch Type)

Branch retinal vein occlusion: Occlusion of a branch of the retinal vein. It is the most common type, with a prevalence of about 2.0%. Occlusion often occurs at arteriovenous crossings.

Central Retinal Vein Occlusion (Central Type)

Central retinal vein occlusion: Occlusion of the central retinal vein at the optic disc. Prevalence is about 0.2%. It tends to be more severe than branch retinal vein occlusion.

HRVO (Hemispheric)

Hemispheric retinal vein occlusion: The veins in the upper or lower half of the retina become blocked. It presents with features intermediate between central retinal vein occlusion and branch retinal vein occlusion.

The peak age of onset is in the 60s to 70s ¹⁾. In young-onset cases, it is important to investigate systemic predisposing factors (such as blood coagulation abnormalities).

Q Can retinal vein occlusion occur in both eyes?

A

It is usually unilateral, but there is a risk of occurrence in the fellow eye. Particularly in central retinal vein occlusion, management of systemic risk factors can help prevent involvement of the other eye.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Sudden vision loss: Often occurs suddenly and unilaterally ¹⁾. Macular edema is the main cause.
• Visual field defect: A sector-shaped visual field defect corresponding to the occluded area occurs. In branch retinal vein occlusion, a superior or inferior altitudinal defect is typical.
• Metamorphopsia: Distortion of the retina due to macular edema causes straight lines to appear wavy.
• Floaters: Occur when vitreous hemorrhage is present.

Clinical Findings

The main findings in the acute phase are shown below ¹⁾.

• Retinal hemorrhage: Flame-shaped or blot hemorrhages along the distribution of the veins. In central retinal vein occlusion, they involve all four quadrants.
• Tortuosity and dilation of retinal veins: The occluded veins appear dilated and tortuous.
• Cotton-wool spots (CWS): Cotton-wool spots due to nerve fiber layer infarction. Suggest the presence of ischemia.
• Macular edema: Main cause of vision loss. Can be confirmed as cystoid macular edema (CME) on OCT.
• Optic disc edema: Seen in central retinal vein occlusion.
• Iris neovascularization (NV): Occurs in about 25% of central retinal vein occlusion cases and causes neovascular glaucoma¹⁾.

Q If vision suddenly drops due to retinal vein occlusion, should I see a doctor immediately?

A

Yes, early consultation as soon as possible is important. Early treatment of macular edema affects visual prognosis. Also, serious complications such as iris neovascularization can progress asymptomatically, so regular follow-up is necessary.

3. Causes and Risk Factors

The major risk factors for retinal vein occlusion are as follows¹⁾.

• Hypertension: The most important risk factor. Strongly associated with both branch retinal vein occlusion and central retinal vein occlusion.
• Arteriosclerosis: Shared adventitia at arteriovenous crossings provides the anatomical basis for occlusion.
• Diabetes: Increases risk through vascular endothelial damage and increased blood viscosity.
• Dyslipidemia/Obesity: Risk factors associated with metabolic syndrome.
• Glaucoma: Thought to involve venous compression at the optic disc.

In 58% of central retinal vein occlusion patients under 50 years old, non-traditional risk factors (such as coagulation abnormalities, autoimmune diseases) other than hypertension and diabetes are found¹⁾. Systemic lupus erythematosus (SLE) increases the risk of retinal vein occlusion by 3.5 times¹⁾.

Patients with retinal vein occlusion have an increased risk of cardiovascular events and all-cause mortality compared to the general population¹⁾. This is one reason why medical management after onset is important.

Prevention and Daily Care

• Properly control hypertension, diabetes, and dyslipidemia.
• Have regular eye exams to detect early changes.
• Smoking increases the risk of retinal vein occlusion, so try to quit.
• If you experience sudden vision changes or visual field defects in one eye, see an ophthalmologist immediately.

4. Diagnosis and Examination Methods

During the examination, the pupillary light reflex is important; in central retinal vein occlusion, a relative afferent pupillary defect (RAPD) may be observed ¹⁾.

The main examination methods are shown below.

Examination	Purpose	Key Points
OCT	Quantification of macular edema	Also used to assess treatment response
Fluorescein angiography (FA)	Evaluation of ischemic areas	PRP indicated when nonperfusion area ≥10 PD 1)
OCTA	Assessment of blood flow and capillaries	Can be performed non-invasively1)

• OCT (Optical Coherence Tomography): Non-invasively evaluates the degree and characteristics of macular edema (cystoid, serous detachment)¹⁾. Also used for quantitative assessment of treatment response.
• Fluorescein Angiography (FA): Evaluates the extent of non-perfusion areas (capillary non-perfusion). In central retinal vein occlusion and hemi-retinal vein occlusion, panretinal photocoagulation (PRP) is indicated when the non-perfusion area is 10 disc diameters (PD) or more¹⁾.
• OCTA (OCT Angiography): Evaluates retinal and choroidal blood flow without the use of contrast agents¹⁾. Useful for assessing non-perfusion areas and detecting neovascularization.

5. Standard Treatment

Anti-VEGF Therapy

First-line treatment: The most important treatment for macular edema. Administered via intravitreal injection.

Approved drugs: Ranibizumab, aflibercept, faricimab (all covered by insurance).

Steroid Therapy

Second-line treatment: Considered when response to anti-VEGF is insufficient.

Drugs: Intravitreal triamcinolone injection or dexamethasone intravitreal implant (Ozurdex).

Laser Photocoagulation

Macular edema due to branch retinal vein occlusion: Grid laser photocoagulation has been shown effective in the BVOS study. Currently, anti-VEGF is the mainstay.

Neovascularization/ischemia: PRP (panretinal photocoagulation) is indicated for iris neovascularization in central retinal vein occlusion and hemi-retinal vein occlusion ¹⁾.

Intravitreal Anti-VEGF Injection

This is the current standard treatment for macular edema ¹⁾. Available agents are as follows:

• Ranibizumab (Lucentis): Anti-VEGF-A antibody fragment. It has insurance coverage for macular edema due to retinal vein occlusion.
• Aflibercept (Eylea): A fusion protein that inhibits VEGF-A, VEGF-B, and PlGF.
• Faricimab (Vabysmo): A bispecific antibody that simultaneously inhibits VEGF-A and Ang-2 (angiopoietin-2). It is expected to allow longer dosing intervals.

Laser Photocoagulation

• Grid photocoagulation (branch retinal vein occlusion): The Branch Vein Occlusion Study (BVOS) reported that grid photocoagulation is effective for macular edema persisting for 3 months or more. Currently, anti-VEGF therapy is the mainstay.
• Grid photocoagulation (central retinal vein occlusion): The Central Vein Occlusion Study (CVOS) did not confirm visual improvement with grid photocoagulation for macular edema due to central retinal vein occlusion. Anti-VEGF therapy is the first-line treatment for macular edema in central retinal vein occlusion.
• Panretinal photocoagulation (PRP): Indicated for central retinal vein occlusion and hemi-retinal vein occlusion when there is extensive non-perfusion area, or when iris or angle neovascularization appears ¹⁾. It is performed to prevent neovascular glaucoma.

Precautions in Treatment

• Intravitreal injection carries a risk of infection (endophthalmitis). Redness, eye pain, or decreased vision the day after injection require attention.
• Intravitreal steroid injection carries risks of increased intraocular pressure and cataract progression. Regular intraocular pressure measurement is necessary.
• Iris neovascularization can progress asymptomatically and lead to neovascular glaucoma. Regular gonioscopy is recommended in central retinal vein occlusion ¹⁾.

Q How many anti-VEGF injections are needed?

A

The degree of macular edema and response to treatment vary greatly among individuals. Initially, injections are given once a month, and a treat-and-extend method is used to lengthen the interval as edema improves. With faricimab, extension up to 16-week intervals is expected.

6. Pathophysiology and Detailed Mechanism

The occlusion mechanism of retinal vein occlusion involves anatomical, hematological, and vascular wall factors ¹⁾.

Occlusion at the arteriovenous crossing (branch retinal vein occlusion): Retinal arteries and veins share the adventitia at the crossing. Arteriosclerotic thickening of the arterial wall compresses the vein from the outside, causing turbulence, endothelial damage, and thrombus formation ¹⁾.

Occlusion at the optic nerve head (central retinal vein occlusion): Shear forces and vascular wall changes at the lamina cribrosa are thought to cause occlusion.

After occlusion, the following course occurs:

• Increased venous pressure and extravasation: Occlusion raises hydrostatic pressure, causing plasma components to leak into the retina.
• VEGF production: In response to retinal ischemia, VEGF is released from retinal pigment epithelium and Müller cells ¹⁾.
• Formation of macular edema: VEGF-dependent increased vascular permeability leads to cystoid macular edema.
• Neovascularization: Persistent ischemic stimulation leads to new blood vessels in the retina, iris, and angle ¹⁾.
• Formation of collateral circulation: In the chronic phase, collateral vessels develop as alternatives to the occluded vein, and macular edema may resolve spontaneously.

7. Latest Research and Future Prospects

For patients: Please read this

The following content is currently under research or in clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Wide-field fundus photography and wide-field FA

The widespread use of wide-angle fundus photography and ultra-widefield fluorescein angiography (UWFA) has enabled more accurate evaluation of peripheral retinal nonperfusion areas ¹⁾. This is expected to improve the accuracy of treatment indication decisions.

Advances in OCTA

OCTA (OCT angiography) allows evaluation of retinal blood flow without the need for contrast agents ¹⁾. With improved resolution, quantitative assessment of capillary nonperfusion areas and macular capillary density is becoming possible. It is expected to serve as an objective indicator of anti-VEGF treatment efficacy.

Faricimab and Ang-2 Targeted Therapy

Faricimab is a bispecific antibody that simultaneously inhibits VEGF-A and Ang-2. Ang-2 reduces vascular stability and, in coordination with VEGF, promotes vascular permeability and neovascularization. Inhibition of Ang-2 is expected to improve treatment outcomes in cases where VEGF inhibition alone is insufficient.

The 2025 revised PPP by the AAO Retina/Vitreous Panel identifies the development of evidence on the cost-effectiveness of anti-VEGF therapy as a challenge ¹⁾. Continued research is also needed on the relationship between long-term treatment adherence and visual outcomes.

Q How is faricimab different from conventional anti-VEGF drugs?

A

While conventional drugs inhibit only VEGF-A, faricimab inhibits both VEGF-A and Ang-2. Since Ang-2 is involved in vascular destabilization, simultaneously suppressing it is expected to prolong dosing intervals and stabilize treatment effects.

Q Can retinal vein occlusion be cured? What is the prognosis?

A

Branch retinal vein occlusion may improve spontaneously due to the development of collateral circulation, but if macular edema persists, visual acuity decline continues. Central retinal vein occlusion generally has a poor prognosis, with more than half of ischemic cases experiencing vision loss. Anti-VEGF therapy has improved visual outcomes, but regular ongoing treatment is often necessary.

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8. References

1. AAO Retina/Vitreous Panel. Retinal Vein Occlusions PPP. Ophthalmology. 2025;132(2):P314-P345.