Preoperative Intravitreal Bevacizumab Use as an Adjuvant to Diabetic Vitrectomy: Histopathologic Findings and Clinical Implications

Abstract

To evaluate the effects of intervals between preoperative intravitreal injection of bevacizumab (IVB) and surgery on the components of removed diabetic fibrovascular proliferative membranes. Interventional, consecutive, prospective, comparative case series. A total of 52 eyes of 49 patients with active diabetic fibrovascular proliferation with complications necessitating vitrectomy. Participant eyes that had IVB were divided into 8 groups in which vitreoretinal surgery was performed at days 1, 3, 5, 7, 10, 15, 20, and 30 postinjection. A group of eyes with the same diagnosis and surgical intervention without IVB injection was used for comparison. In all eyes, proliferative membrane specimens obtained during vitrectomy were sent for histopathologic examination using hematoxylin-eosin stain, immunohistochemistry (CD34 and smooth muscle actin), and Masson's trichrome stain. Comparative analysis of different components of the fibrovascular proliferation (CD34, smooth muscle actin, and collagen) among the study groups. Pan-endothelial marker CD34 expression levels starting from day 5 postinjection were significantly less than in the control group (P < 0.001), with minimum expression (1+) in all specimens removed at or after day 30 postinjection. Positive staining for smooth muscle actin was barely detected in the control eyes at day 1, and consistently intense at day 15 and beyond (P < 0.001). The expression level of trichrome staining was significantly high at day 10, compared with control eyes (P < 0.001), and continued to increase at subsequent surgical time points. A profibrotic switch was observed in diabetic fibrovascular proliferation after IVB, and our results suggest that at approximately 10 days post-IVB the vascular component of proliferation is markedly reduced, whereas the contractile components (smooth muscle actin and collagen) are not yet abundant.