Anti-VEGF Trials in Retinal Vein Occlusion

Anti-VEGF trials in retinal vein occlusion changed practice in the 2010s.

The acronyms are now part of everyday clinic conversation.

They showed that injections improve vision in macular edema from branch and central occlusion.

They refined how often treatment is needed.

A short summary of each trial helps to place the evidence.

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Why Anti-VEGF Trials in Retinal Vein Occlusion Mattered

Before anti-VEGF drugs, the options for macular edema in vein occlusion were observation, grid laser for branch occlusion, and steroids (see grid laser for branch vein occlusion).

Central vein occlusion had no proven treatment for vision, apart from the control of complications.

Vascular endothelial growth factor is raised in ischemic retina.

It increases vascular permeability, so blocking it was a logical approach (see anti-VEGF therapy).

Ranibizumab: BRAVO and CRUISE in anti-VEGF Trials in Retinal Vein Occlusion

BRAVO studied branch occlusion, and CRUISE studied central occlusion.

Patients were randomized to monthly ranibizumab at two doses or to sham injection for six months, followed by a period of as-needed treatment.

Treated eyes gained about 16 to 18 letters in BRAVO and about 12 to 15 letters in CRUISE at six months, whereas sham eyes gained far less.

The gains were largely maintained in the second half of the first year with fewer injections.

These trials led to approval of ranibizumab for macular edema after vein occlusion (see the references).

Aflibercept: COPERNICUS, GALILEO, and VIBRANT

COPERNICUS and GALILEO tested aflibercept in central occlusion with monthly injections for six months.

Aflibercept eyes gained about 17 to 18 letters, compared with about 1 to 4 letters in sham eyes, at 24 weeks.

VIBRANT compared aflibercept with grid laser in branch occlusion, and found that the injection group gained more letters at 24 weeks, about 17 versus 12, with a significant advantage in the proportion that gained at least 15 letters.

Bevacizumab Versus Aflibercept: SCORE2 in anti-VEGF Trials in Retinal Vein Occlusion

SCORE2 asked whether the cheaper drug bevacizumab was as good as aflibercept in central or hemiretinal occlusion.

Bevacizumab was noninferior to aflibercept at six months, on the margin chosen.

The two had similar results in terms of vision and safety (see the references).

The trial supports the use of bevacizumab as a lower-cost option when aflibercept is not available or affordable.

Steroid Trials

Meanwhile, the SCORE study compared triamcinolone with standard care and found a benefit for central occlusion, but with side effects of cataract and raised pressure.

Also, the dexamethasone implant also showed benefit in the GENEVA trials (see dexamethasone intravitreal implant).

Steroids are used as alternatives or second-line treatments, particularly in patients unsuitable for repeated injections.

Anti-VEGF Trials in Retinal Vein Occlusion: Treatment Patterns After the Trials

• Loading phase: monthly injections until the macula is dry or vision stops improving, often three to six doses
• Maintenance: as-needed or treat-and-extend, adapting to recurrence (see treat-and-extend regimen)
• Retreatment: many eyes need fewer injections in the second year, and some can stop treatment
• Rescue laser: added in some protocols for persistent edema in branch occlusion

Limits of the Evidence

• Most trials followed patients for six months to a year, with extension to two years, and long-term outcomes are less certain
• Ischemic occlusion carries a risk of neovascularization even with treatment, so surveillance is needed (see retinal neovascularization)
• Trials excluded some patients, such as those with poor perfusion or recent surgery
• Vision gains in real-world practice are often smaller than in trials, because of delays and undertreatment

Practical Summary

Anti-VEGF therapy is first-line for macular edema from vein occlusion, with steroids as an alternative.

Monitor closely, treat early, and extend intervals as the macula dries.

Investigate systemic risk factors in parallel (see retinal vein occlusion workup).

Which Drug to Choose?

The trials show that ranibizumab, aflibercept, and bevacizumab all improve vision, and the choice often depends on cost, access, and the patient’s response.

Many services begin with bevacizumab, and switch to another drug if there is an inadequate response after several injections.

Patients with persistent edema may benefit from a change of agent, a steroid implant, or the addition of laser.

Practical Pointers

Do not stop treatment too early, because recurrence is common in the first year, and monitor for several months after the last injection.

Explain to patients that vision often improves within weeks, but that the full effect may take months, and that results vary with the degree of ischemia.

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References

1. Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study (BRAVO). Ophthalmology. 2010;117:1102-1112.
2. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study (CRUISE). Ophthalmology. 2010;117:1124-1133.
3. Scott IU, VanVeldhuisen PC, Ip MS, et al. Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial. JAMA. 2017;317:2072-2087.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 12: Retina and Vitreous. AAO; current edition.