What are the indications for intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy in patients with Retinal Vein Occlusion (RVO)?

Intravitreal Anti-VEGF Indications in Retinal Vein Occlusion

Anti-VEGF agents are the preferred first-line therapy for macular edema causing vision loss in both branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), with FDA-approved agents including ranibizumab and aflibercept. 1, 2, 3, 2

Primary Indication: Macular Edema with Vision Loss

The core indication for anti-VEGF therapy in RVO is macular edema documented on OCT that causes visual acuity impairment. 1 This represents a strong recommendation based on multiple randomized controlled trials demonstrating superior visual outcomes compared to observation or laser therapy alone.

Evidence Supporting First-Line Use

• For BRVO: Anti-VEGF agents demonstrate superior efficacy over grid laser photocoagulation, with the VIBRANT trial showing significant visual gains with aflibercept compared to laser treatment. 1

• For CRVO: Multiple landmark trials (CRUISE with ranibizumab, COPERNICUS and GALILEO with aflibercept) demonstrated 15-letter gains in 56-60% of treated eyes versus 12-20% with sham injections. 1

• Bevacizumab (off-label) showed comparable efficacy with 15-letter gain in 60% of treated eyes in randomized trials, and SCORE2 demonstrated similar visual outcomes between aflibercept and bevacizumab at 6 months. 1

Secondary Indication: Adjunctive Treatment for Neovascularization

Anti-VEGF agents serve as adjunctive therapy when panretinal photocoagulation (PRP) is insufficient to control retinal or iris neovascularization. 1, 4 While dense peripheral PRP remains the primary treatment for neovascular complications, anti-VEGF provides immediate benefit and may improve the ability to deliver complete laser treatment. 4

Specific Neovascular Scenarios

• Iris neovascularization in CRVO: Initial anti-VEGF treatment before or alongside complete peripheral PRP helps prevent progression to neovascular glaucoma. 4

• Retinal neovascularization in BRVO: Sectoral laser photocoagulation to areas of nonperfusion is primary, but anti-VEGF can be used adjunctively to reduce vitreous hemorrhage risk. 5

Treatment Algorithm Based on RVO Type

For BRVO with Macular Edema:

1. Initiate anti-VEGF therapy (ranibizumab 0.5 mg or aflibercept 2 mg monthly initially) for visual acuity ≤20/40 with macular edema. 1, 5
2. Consider corticosteroids or grid laser only if inadequate response or contraindications to anti-VEGF exist. 1
3. Add sectoral laser if retinal neovascularization develops. 5

For CRVO with Macular Edema:

1. Begin anti-VEGF therapy immediately (same dosing as BRVO) for any vision-threatening macular edema. 1
2. If poor response at 6 months, consider switching agents (e.g., aflibercept if started on bevacizumab) or adding dexamethasone implant. 1
3. Institute complete peripheral PRP if iris or angle neovascularization develops, with anti-VEGF as adjunct. 4

FDA-Approved Dosing Regimens

Aflibercept: 2 mg (0.05 mL) intravitreal injection every 4 weeks (monthly) for RVO-related macular edema. 2

Ranibizumab: Indicated for macular edema following RVO with monthly dosing. 3

Bevacizumab: Remains off-label but widely used with demonstrated efficacy comparable to FDA-approved agents. 1, 6

Critical Timing Considerations

Early treatment initiation is paramount for optimal outcomes. 7 In patients with CRVO presenting with poor visual acuity (worse than 20/320), delays of 30 days or more from symptom onset to first injection predict:

• Significantly worse visual gains (P < 0.0001) 7
• 11-fold higher incidence of neovascular complications (hazard ratio 11.036,95% CI 1.807-67.393) 7

Safety Profile and Risk-Benefit Analysis

Anti-VEGF agents have a favorable risk-to-benefit profile compared to corticosteroids. 1 Key safety considerations:

• Severe adverse events are uncommon: endophthalmitis (0.0-0.9%), retinal detachment, and elevated IOP. 1, 8
• No increased arterial thromboembolic events demonstrated in meta-analyses. 1
• Significantly lower rates of cataract progression (0.9-7.0%) compared to steroids (19.8-35.0%). 8
• Minimal IOP elevation risk compared to corticosteroids (0% requiring treatment vs. 7.0-41.0% with steroids). 8

Common Pitfalls to Avoid

1. Delaying treatment while "observing" in CRVO—this significantly worsens outcomes and increases neovascular risk. 7
2. Using corticosteroids as first-line therapy—reserve for anti-VEGF non-responders or contraindications due to higher cataract and glaucoma risk. 1, 8
3. Inadequate monitoring for neovascularization—monthly assessment of iris/angle is essential in the first 6 months, particularly in CRVO. 5
4. Failing to perform fluorescein angiography—necessary to detect ischemic areas requiring laser treatment. 6

When Corticosteroids May Be Considered

Intravitreal corticosteroids (triamcinolone, dexamethasone implant) should be reserved for: 1

• Inadequate response to anti-VEGF therapy after 6 months
• Contraindications to anti-VEGF (recent thromboembolic events)
• Poor responders requiring rescue therapy (dexamethasone for aflibercept non-responders per SCORE2) 1

However, patients must be counseled about significant risks of cataract progression and IOP elevation requiring treatment. 1, 8