# Retinal Vascular Occlusions: BRVO and CRVO

## Central Retinal Vein Occlusion (CRVO)

### Pathophysiology

Central retinal vein occlusion occurs at or posterior to the lamina cribrosa, where the central retinal vein and central retinal artery share a common adventitial sheath. This shared sheath creates the anatomic substrate for compression. Thrombus formation follows from the classic elements of the Virchow triad: vessel wall compression, turbulent flow, and endothelial damage. The resulting obstruction increases venous pressure throughout the retina, producing hemorrhagic retinopathy, retinal edema, and, in severe cases, widespread retinal ischemia. The most common systemic risk factor is hypertension, followed by diabetes mellitus, hyperlipidemia, glaucoma or ocular hypertension, hypercoagulable states, and hyperviscosity syndromes.

### Classification

| Feature | Non-Ischemic (Perfused) CRVO | Ischemic (Non-Perfused) CRVO |
|---------|------------------------------|------------------------------|
| Proportion | ~75% of cases | ~25% of cases |
| Hemorrhages | Moderate | Extensive (all 4 quadrants) |
| Visual acuity | Often 20/40 or better | Usually 20/200 or worse |
| Cotton-wool spots | Few | Prominent |
| RAPD | Absent | Present |
| FFA non-perfusion | < 10 disc areas | > 10 disc areas |
| NVG risk | Low | ~60% if untreated |
| Prognosis | Relatively favorable | Poor; "100-day glaucoma" risk |
| Conversion | ~15% convert to ischemic within 3 years | N/A |

CRVO is classified into two forms based on the degree of retinal ischemia. Non-ischemic (perfused) CRVO accounts for approximately 75% of cases and presents with fewer hemorrhages, mild disc edema, and well-maintained retinal perfusion on fluorescein angiography. Visual acuity is often 20/40 or better, and the prognosis is relatively favorable. However, approximately 15% of non-ischemic cases convert to the ischemic form within three years, making ongoing surveillance essential.

Ischemic (non-perfused) CRVO accounts for the remaining 25% of cases and presents a dramatically different clinical picture. Extensive hemorrhages fill all four quadrants, cotton-wool spots are prominent, and disc edema is marked. Visual acuity is usually 20/200 or worse. Fluorescein angiography reveals more than ten disc areas of capillary non-perfusion, and a relative afferent pupillary defect is present. Ischemic CRVO carries a high risk of neovascular complications, including neovascularization of the iris and neovascular glaucoma -- the so-called "100-day glaucoma" because it classically develops approximately three months after the vascular event.

### Clinical Features

Patients present with sudden painless vision loss, frequently noticed upon waking. Funduscopic examination reveals dilated, tortuous veins in all four quadrants with flame-shaped and dot-blot hemorrhages throughout the posterior pole. Cotton-wool spots, disc edema, and macular edema are commonly present. In severe ischemic CRVO, the fundus takes on the dramatic appearance described as "blood and thunder."

<image>Fundus photographs comparing non-ischemic CRVO with moderate hemorrhages and dilated veins versus ischemic CRVO with extensive four-quadrant hemorrhages, cotton-wool spots, and disc edema</image>

### Workup

Systemic evaluation should include blood pressure measurement, fasting glucose or hemoglobin A1c, lipid panel, and complete blood count. In patients under 50 years of age or those with bilateral CRVO, a hypercoagulable workup should be considered, including antiphospholipid antibodies, factor V Leiden, protein C and S levels, antithrombin III, and homocysteine. Intraocular pressure should be checked, as glaucoma is both a risk factor for and a complication of CRVO. Fluorescein angiography assesses capillary non-perfusion and helps classify the occlusion as ischemic or non-ischemic. OCT quantifies macular edema, which is the most common cause of vision loss.

### Management

#### Macular Edema (Most Common Cause of Vision Loss)

Anti-VEGF therapy is the first-line treatment for macular edema associated with CRVO. The CRUISE trial demonstrated that monthly ranibizumab injections over six months produced significant visual acuity improvement. The COPERNICUS and GALILEO trials established the efficacy of aflibercept for CRVO-associated macular edema. The SCORE2 trial showed that aflibercept and bevacizumab are comparably effective, simplifying clinical decision-making. After a loading phase of monthly injections, a treat-and-extend protocol is the standard maintenance approach.

Intravitreal corticosteroids serve as second-line therapy. The dexamethasone implant (Ozurdex) was shown in the GENEVA trial to be effective, though it carries risks of IOP elevation and cataract progression. Corticosteroids are most appropriate in pseudophakic eyes or in patients who do not respond adequately to anti-VEGF therapy.

#### Neovascular Complications

Monitoring for neovascularization of the iris is essential at every follow-up visit, using undilated gonioscopy and careful slit-lamp examination of the iris. In ischemic CRVO, neovascular glaucoma develops in approximately 60% of untreated eyes. Panretinal photocoagulation should be applied when neovascularization is detected, but not prophylactically -- the Central Vein Occlusion Study demonstrated no benefit from prophylactic PRP. When neovascular glaucoma develops, combined anti-VEGF injection and PRP is the recommended approach.

## Branch Retinal Vein Occlusion (BRVO)

### Pathophysiology

Branch retinal vein occlusion occurs at arteriovenous crossings where a retinal artery and vein share a common adventitial sheath. The artery, being more rigid, compresses the underlying vein at these crossings, producing turbulence, endothelial damage, and ultimately thrombosis. The superotemporal arcade is the most common site, accounting for 63% of cases. Risk factors mirror those of CRVO, with hypertension being the most important.

### Clinical Features

BRVO produces a distinctive sector-shaped pattern of hemorrhage that follows the distribution of the affected retinal vein. Flame-shaped and dot-blot hemorrhages are confined to the affected sector, in contrast to the four-quadrant involvement seen in CRVO. Macular edema develops when the affected branch drains through the macula, and cotton-wool spots may be present in areas of ischemia. Visual acuity depends on the degree of macular involvement.

### Classification

Three subtypes are recognized based on the level of venous obstruction. Major BRVO involves a primary branch vein and produces more extensive retinal involvement. Macular BRVO involves a smaller venule draining the macula, affecting a smaller retinal area but with disproportionate visual impact due to direct macular involvement. Hemiretinal vein occlusion involves either the superior or inferior trunk of the central retinal vein, producing hemorrhages in the upper or lower half of the fundus; it behaves clinically more like CRVO than BRVO and carries a higher risk of neovascular complications.

### Management

#### Macular Edema

Anti-VEGF therapy is first-line treatment for BRVO-associated macular edema. The BRAVO trial demonstrated that ranibizumab was superior to sham injection. The VIBRANT trial showed aflibercept to be superior to grid laser. The SCORE2 trial confirmed that bevacizumab and aflibercept are comparably effective, and treat-and-extend protocols are the standard approach.

Grid laser photocoagulation, which was established as effective by the Branch Vein Occlusion Study for eyes with visual acuity of 20/40 or worse, now serves as a second-line or adjunctive treatment. Laser should be applied only after hemorrhage has cleared sufficiently to identify the area of leakage. The dexamethasone implant is an option for pseudophakic eyes or anti-VEGF treatment failures.

#### Neovascularization

Neovascularization develops in approximately 60% of ischemic BRVOs. When neovascularization is detected, sector PRP is applied to the ischemic area, as recommended by the Branch Vein Occlusion Study. Prophylactic PRP has not been shown to provide benefit and is not recommended.

<image>Fundus photograph of superotemporal branch retinal vein occlusion showing sector-shaped flame hemorrhages, dilated tortuous veins, and macular edema limited to the distribution of the affected branch vein</image>

## Hemiretinal Vein Occlusion

### Features

Hemiretinal vein occlusion involves either the superior or inferior trunk of the central retinal vein, producing hemorrhages confined to the upper or lower half of the fundus. Despite its branch-like distribution, it behaves clinically more like CRVO, with a higher risk of neovascular complications than typical BRVO. Management follows the same principles as CRVO.

## Central Retinal Artery Occlusion (Brief Overview for Comparison)

Central retinal artery occlusion presents as acute painless vision loss, typically to the count-fingers level or worse. The classic funduscopic finding is the cherry-red spot, which results from the intact choroidal circulation being visible through the thin foveola, contrasted against the surrounding pale, ischemic inner retina. Box-car segmentation of the blood column within retinal arterioles -- also called cattle-trucking -- may be observed, and a relative afferent pupillary defect is present. Treatment options, all with limited evidence, include ocular massage, anterior chamber paracentesis, and intravenous thrombolysis with tissue plasminogen activator if the patient presents within hours of onset. In any patient over 50, an erythrocyte sedimentation rate and C-reactive protein must be obtained urgently to rule out giant cell arteritis as the underlying cause.

## Prognostic Factors

### CRVO

The initial visual acuity at presentation is the single best predictor of the final visual outcome in CRVO. The distinction between ischemic and non-ischemic disease is the most clinically important classification, as it determines the risk of neovascular complications. Younger patients under 50 generally have a better prognosis but warrant a hypercoagulable workup. The presence of a relative afferent pupillary defect strongly suggests ischemic CRVO.

### BRVO

BRVO generally carries a better prognosis than CRVO. The visual outcome depends primarily on whether the macula is involved. Over months, collateral vessels may form, gradually improving venous drainage from the affected sector. However, chronic macular edema, if left untreated, leads to progressive photoreceptor damage and permanent vision loss.

<image>Fluorescein angiography of ischemic CRVO showing extensive areas of capillary non-perfusion (dark areas), dilated leaking capillaries, and optic disc hyperfluorescence</image>

## Clinical Pearls

Hypertension is the number one risk factor for both BRVO and CRVO, and blood pressure should be checked in every patient presenting with a retinal vein occlusion. When CRVO occurs in a young patient, the differential diagnosis should include hypercoagulable states, autoimmune disease, and oral contraceptive use. Prophylactic PRP should not be performed in either CRVO (per the CVOS) or BRVO (per the BVOS); laser treatment is applied only after neovascularization has been documented. The concept of "100-day glaucoma" should prompt vigilant examination for rubeosis at every CRVO follow-up visit for at least six months. Non-ischemic CRVO can convert to ischemic disease, making serial monitoring with fluorescein angiography or OCTA essential. The SCORE2 trial simplified clinical practice by showing that bevacizumab and aflibercept are equally effective for retinal vein occlusion-associated macular edema. Collateral vessels typically develop over six to twelve months in BRVO, and their presence on examination suggests improved venous drainage. Both eyes should always be examined, as bilateral CRVO raises suspicion for systemic hyperviscosity or hypercoagulability.

## References

- Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol. 1997;115(4):486-491.
- Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98(3):271-282.
- Brown DM, et al. Ranibizumab for macular edema following central retinal vein occlusion (CRUISE). Ophthalmology. 2010;117(6):1124-1133.
- Scott IU, et al. SCORE2: aflibercept, bevacizumab, or sham for macular edema from central retinal vein occlusion. Ophthalmology. 2017;124(7):920-921.
- American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous.