Document Detail

Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion.
MedLine Citation:
PMID:  23260261     Owner:  NLM     Status:  MEDLINE    
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.
Peter A Campochiaro; Robert B Bhisitkul; Howard Shapiro; Roman G Rubio
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-12-20
Journal Detail:
Title:  Ophthalmology     Volume:  120     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-21     Revised Date:  2013-12-30    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  795-802     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Antibodies, Monoclonal, Humanized / administration & dosage,  therapeutic use*
Disease Progression
Double-Blind Method
Fluorescein Angiography
Follow-Up Studies
Fundus Oculi
Macular Edema / drug therapy*,  etiology,  metabolism
Retina / pathology*
Retinal Vein Occlusion / complications,  drug therapy*,  metabolism
Retrospective Studies
Treatment Outcome
Vascular Endothelial Growth Factor A / drug effects,  metabolism*
Reg. No./Substance:
0/Antibodies, Monoclonal, Humanized; 0/Vascular Endothelial Growth Factor A; 0/ranibizumab
Comment In:
Klin Monbl Augenheilkd. 2013 Nov;230(11):1078, 1080

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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