Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion

PA Campochiaro, RB Bhisitkul, H Shapiro, RG Rubio - Ophthalmology, 2013 - Elsevier
PA Campochiaro, RB Bhisitkul, H Shapiro, RG Rubio
Ophthalmology, 2013Elsevier
OBJECTIVE: Central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO)
causes hypoperfusion, high levels of vascular endothelial growth factor (VEGF), macular
edema, and loss of vision. Many patients also show areas of complete closure of retinal
vessels (retinal nonperfusion [RNP]) that increase over time. The objective was to assess the
effect of blocking VEGF on progression of RNP. DESIGN: Retrospective analysis of
prospectively collected data from 2 randomized, sham injection-controlled, double-masked …
OBJECTIVE
Central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) causes hypoperfusion, high levels of vascular endothelial growth factor (VEGF), macular edema, and loss of vision. Many patients also show areas of complete closure of retinal vessels (retinal nonperfusion [RNP]) that increase over time. The objective was to assess the effect of blocking VEGF on progression of RNP.
DESIGN
Retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.
PARTICIPANTS
A total of 392 and 397 patients with macular edema due to CRVO or BRVO.
METHODS
An independent reading center measured the area of RNP on fluorescein angiograms (FAs) in 2 phase III trials investigating the effect of ranibizumab (RBZ; Lucentis; Genentech, Inc, South San Francisco, CA) in patients with CRVO or BRVO.
MAIN OUTCOME MEASURES
The percentage of patients with no posterior RNP at months 0, 3, 6, 9, and 12.
RESULTS
There was no difference among treatment groups at baseline, but at the month 6 primary end point the percentage of patients with CRVO and no RNP was significantly greater in the RBZ groups (0.3 mg, 82.0%, P = 0.0092; 0.5 mg, 84.0%, P = 0.0067) versus the sham group (67.0%). Reperfusion of nonperfused retina was rare (1%) in sham-treated patients with CRVO, but occurred in 6% to 8% of patients with CRVO treated with RBZ (30% of those who had RNP and could improve). Results in patients with BRVO mirrored those in patients with CRVO. Crossover to 0.5 mg RBZ from sham at month 6 halted the progression of RNP and resulted in improvement in both CRVO and BRVO.
CONCLUSIONS
Treatment with RBZ did not worsen RNP in patients with RVO, but rather reduced its occurrence compared with sham. These data provide an important new insight regarding the pathogenesis of RVO; the initial vein occlusion is a precipitating event that causes baseline ischemia and release of VEGF, which then contributes to progression of RNP and thus worsening of ischemia. Timely, aggressive blockade of VEGF prevents the worsening of RNP, promotes reperfusion, and eliminates a positive feedback loop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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