Subjects

• Inclusion criteria:
  • Visual impairment due to macular edema secondary to CRVO diagnosed less than 6 months prior to screening
  • BCVA 78–23 letters (approx. 20/32 to 20/320)
• Exclusion criteria:
  • Ocular disorders in the study eye that prevent response to or assessment of study treatment (including significant diabetic retinopathy)
  • Active intraocular inflammation in study eye
  • Uncontrolled glaucoma in the study eye (IOP>25mmHg on medication)
  • Previous anti-VEGF, intraocular/periocular steroids, macular/peripheral laser photocoagulation within 3 months prior to baseline
  • Intraocular surgery within 3 months prior to baseline
  • Vitreoretinal surgery

Randomization Scheme/Study Interventions

• After 6 initial monthly injections with intravitreal brolucizumab 6mg or aflibercept 2mg (loading phase), subjects entered a one-year individualized flexible treatment (IFT) phase.
• During the IFT phase, disease stability was assessed monthly and subjects received either an active or sham injection.

Results

• The study was terminated by the sponsor due to increased incidences of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, in patients dosed brolucizumab 6mg every 4 weeks beyond 3 initial doses.
• Prior to termination, there were two cases of reported retinal artery occlusion and retinal vasculitis (2/247 eyes, 0.81%) in the brolucizumab group, compared to none in the aflibercept group.

Conclusions

• RAVEN was a phase 3 study comparing intravitreal brolucizumab 6mg to aflibercept 2mg in patients with macular edema due to CRVO.
• The study was terminated due to increased incidence of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, in patients dosed brolucizumab 6mg every 4 weeks beyond 3 initial doses.