Yonsei Med J.  2011 Jan;52(1):151-157. 10.3349/ymj.2011.52.1.151.

Effect of Intravitreal Bevacizumab on Vascular Endothelial Growth Factor Expression in Patients with Proliferative Diabetic Retinopathy

• Chung EJ
• Kang SJ
• Koo JS
• Choi YJ
• Grossniklaus HE
• Koh HJ

• KMID: 1106450
• DOI: http://doi.org/10.3349/ymj.2011.52.1.151

Abstract

PURPOSE
To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco, CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR).
MATERIALS AND METHODS
Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done.
RESULTS
The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043).
CONCLUSION
Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.

Keyword

Intravitreal bevacizumab; proliferative diabetic retinopathy; vascular endothelial growth factor

MeSH Terms

Adult
Angiogenesis Inhibitors/*therapeutic use
Antibodies, Monoclonal/*therapeutic use
Diabetic Retinopathy/*drug therapy/*metabolism
Female
Humans
Immunohistochemistry
Male
Middle Aged
Vascular Endothelial Growth Factor A/*metabolism

Figure

• 

  Fig. 1 Representative fundus photographs and histopathologic findings. (A) Group 1. A fibrotic fibrovascular membrane can be seen in this fundus photo. This section of excised tissue shows sparsely vascularized fibrovascular tissue in H&E staining. (B) Group 2 with regression of active PDR. Regressed NVD, large caliber vessels and gliosis are evident. Sparsely vascularized tissue is present in H&E staining. (C) Group 2 with active PDR. (D) Group 3. Proliferative fibrovascular membranes and preretinal hemorrhage can be seen. H&E staining shows highly vascularized tissue (original magnification × 400). PDR, proliferative diabetic retinopathy; NVD, neovascular at the disc.

• 

  Fig. 2 Immunohistochemistry for vascular endothelial growth factor (VEGF) expression. (A) Group 1. Weak immunoreactivity to VEGF is observed in fibrovascular tissue. (B) Group 2 with regression of active proliferative diabetic retinopathy (PDR). The immunoreactivity to VEGF shows intermediate staining in vascular endothelial cells surrounding the vascular lumen. (C) Group 2 with active PDR (D) Group 3. Strong immunoreactivity to VEGF is shown (original magnification × 400).

• 

  Fig. 3 Immunohistochemistry for CD31. (A) Group 1. CD31-positive blood vessels are barely visible in fibrovascular tissue. (B) Group 2 with regression of active PDR. Vascular lumen with CD31-positive endothelial cells is visible. (C) Group 2 with active PDR. (D) Group 3. Highly vascularized tissue with the vascular lumen surrounded by CD31-positive cells (original magnification × 400).

• 

  Fig. 4 Immunohistochemistry for CD68. (A) Group 1. CD68-positive cells are barely visible in fibrovascular tissue. (B) Group 2. A significant increase in CD68-positive cells can be seen when compared with (A). (C) Group 3. Moderate increase in CD68-positive cells can be seen (original magnification × 400).

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