Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin)

Abstract

Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions; however, corneal avascularity can be compromised by pathologic conditions that negate the cornea's "angiogenic privilege." The clinical relevance of corneal neovascularization has long been recognized, but management of this condition has been hindered by a lack of safe and effective therapeutic modalities. Herein, the etiology, epidemiology, pathogenesis, and treatment of corneal neovascularization are reviewed. Additionally, the authors' recent findings regarding the clinical utility of topical ranibizumab (Lucentis®) and bevacizumab (Avastin®) in the treatment of corneal neovascularization are summarized. These findings clearly indicate that ranibizumab and bevacizumab are safe and effective treatments for corneal neovascularization when appropriate precautions are observed. Although direct comparisons are not conclusive, the results suggest that ranibizumab may be modestly superior to bevacizumab in terms of both onset of action and degree of efficacy. In order to justify the increased cost of ranibizumab, it will be necessary to demonstrate meaningful treatment superiority in a prospective, randomized, head-to-head comparison study.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1

Clinical appearance of corneal neovasculariztion (NV). Superficial stromal NV, deep stromal NV, and corneal scarring secondary to recurrent herpes simplex virus (HSV) keratitis.

Figure 2

Corneal penetration of topical bevacizumab. Immunohistochemical staining seven days after the initiation of topical bevacizumab 1% treatment, 3 times per day, in a normal cornea with intact epithelium (A), and a neovascular cornea (B). Immunoreactivity to bevacizumab was limited to the superficial epithelial layers of normal corneas (A), whereas immunoreactivity to bevacizumab was found in all layers of most neovascularized corneas (B) (×200).

Figure 3

Primary metrics of treatment efficacy. (A) Neovascular area (NA), ie, the area of the corneal vessels; (B) vessel caliber (VC), i.e., the mean corneal vessel diameter; and (C) invasion area (IA), ie, the fraction of the cornea into which vessel invasion occurs.

Figure 4

Summary and comparison of the primary study metrics. (A) Neovascular area (NA): the ranibizumab treated cohort experienced a significant decrease by week 3, while the bevacizumab treated cohort required 6 weeks to experience a significant decrease; (B) vessel caliber (VC): ranibizumab treated patients experienced an earlier significant reduction (3 weeks) than bevacizumab treated patients (12 weeks); (C) invasion area (IA): neither medication produced a significant decrease at any time point. (*P ≤ 0.05 as compared to baseline measures.)