Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema.
OBJECTIVE
To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME).


METHODS
Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.


METHODS
Six hundred sixty-six patients with DME.


METHODS
An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials.


METHODS
The percentage of patients with no posterior RNP.


RESULTS
The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise.


CONCLUSIONS
Just as high VEGF levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with DME, suggesting that regardless of the underlying disease process, high levels of VEGF can cause closure of retinal vessels. However, our data also suggest that VEGF-induced worsening of retinal perfusion in DME is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. Thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with DME.
The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu.
Peter A
PA
Campochiaro
Retina Consultants Houston, Houston, Texas.
Charles C
CC
Wykoff
Genentech, Inc, South San Francisco, California.
Howard
H
Shapiro
Genentech, Inc, South San Francisco, California.
Roman G
RG
Rubio
Genentech, Inc, South San Francisco, California.
Jason S
JS
Ehrlich
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D012039:Regional Blood Flow / Q000187:drug effects; D012170:Retinal Vein Occlusion / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab