Fibrous membranes in diabetic retinopathy and bevacizumab.
OBJECTIVE
The purpose of this study was to determine the histopathologic characteristics of bevacizumab-treated human proliferative diabetic retinopathy (PDR) membranes with particular regard to membrane vasculature as a step toward addressing the effects of the drug on PDR membranes. Intravitreous injection of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, has recently been advocated as an adjunct in surgery for PDR. In this context, a clinically observed decrease in PDR epiretinal membrane vascularity (vascular regression) occurs from 24 hours to 48 hours after injection, but the exact mechanisms of drug action are unknown.


METHODS
A consecutive series of seven PDR membrane specimens that had been removed sequentially from seven bevacizumab-treated patients were studied retrospectively. The membrane specimens were examined using light microscopic methods, including immunohistochemistry.


RESULTS
Five of the seven membranes were clinically avascular (one contained "ghost" vessels) and did not hemorrhage during excision. Of these 5 specimens, which included 1 removed 7 days after a total of 6 intravitreous injections of 1.25 mg bevacizumab, 4 contained histologically detectable capillaries (1 did not). These blood vessels were lined by endothelial cells as determined by immunohistochemistry for the endothelial markers CD31 and CD34. The two remaining membranes were clinically and histologically still vascularized despite bevacizumab treatment. All the specimens also contained smooth muscle actin-containing fibroblastic cells within the collagenous stroma.


CONCLUSIONS
The findings do not support the concept that the clinical phenomenon of vascular regression in PDR membranes after bevacizumab injection in the vitreous is resulting from obliteration of the membrane blood vessels. Another mechanism appears to be involved in at least some patients, possibly a vasoconstrictive response. Such a mechanism might explain reversal of the effects of bevacizumab that has been reported after this treatment.
Pattwell
David M
DM
Unit of Ophthalmology, School of Clinical Sciences, University of Liverpool, Liverpool, UK. david.pattwell@manchester.ac.uk
Stappler
Theodor
T
Sheridan
Carl
C
Heimann
Heinrich
H
Gibran
Syed K
SK
Wong
David
D
Hiscott
Paul
P
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34 / Q000378:metabolism; D001485:Basement Membrane / Q000098:blood supply / Q000473:pathology*; D000068258:Bevacizumab; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D007124:Immunoenzyme Techniques; D007267:Injections; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity; D014822:Vitreous Body
C541116:ACTA2 protein, human; D000199:Actins; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab