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.

Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model

“…Steroids have been shown to have an inhibitory effect on vessel caliber in a chorioallantoic membrane model (McKay et al, 2008) and in a clinical study in patients with diabetic macular edema (Wickremasinghe et al, 2008), indicating an inhibitory effect of steroids on inflammatory cytokines inducing vessel expansion. The ability of anti-VEGF treatment to reduce mature vessel caliber has been demonstrated after topical instillation of bevacizumab in clinical studies König et al, 2009;Stevenson et al, 2012), an effect likely arising from blocking the permeability properties of VEGF.…”

“…Generally, the penetration of topically instilled dexamethasone into the cornea is known from clinical experience and earlier experimental studies (Bessonova et al, 2011;Hoffart et al, 2010;Hos et al, 2011). Topical anti-VEGF antibodies have similarly shown good penetration into the cornea, particularly after local disruption of the epithelial barrier and induction of inflammation and angiogenesis (Rocher et al, 2011;Stevenson et al, 2012;Yoeruek et al, 2008). In the present study, RT-PCR also revealed a significant effect on many cytokines belonging to inflammatory and angiogenic pathways as early as 24h, indicating the rapid effect of the topical treatments.…”

Evaluation of the Additive Effect of Bevacizumab Eye Drops to Mitomycin C in Primary Pterygium

“…Another study by Alhammami et al [17] concluded that subconjunctival Bevacizumab is of benefit in cases of recurrent pterygium. The subconjunctival injection carries the potential risk of systemic complications such as gastrointestinal perforation, hypertension, arteriolar hemorrhage, impaired wound healing, bleeding, endophthalmitis, and arterial thromboembolic events Therefore, it has been suggested that topical instillation is the best route of Bevacizumab administration because it provides both safety and efficacy [18,19].…”

“…Another study by Alhammami et al [17] concluded that subconjunctival Bevacizumab is of benefit in cases of recurrent pterygium. The subconjunctival injection carries the potential risk of systemic complications such as gastrointestinal perforation, hypertension, arteriolar hemorrhage, impaired wound healing, bleeding, endophthalmitis, and arterial thromboembolic events Therefore, it has been suggested that topical instillation is the best route of Bevacizumab administration because it provides both safety and efficacy [18,19].The dose of topical bevacizumab was debated by many authors. An in vitro study conducted by Park et al [20] found that both metabolic activity and viability of primary and recurrent pterygium human Tenon fibroblasts (HTF's) are inhibited by bevacizumab in a dose-dependent manner, especially at concentrations greater than 7.5 mg/ml.…”

Corneal Neovascularization and Treatment: Review

“…55,56 Yapılan çalışmalarda ranibizumab'ın bevacizumab ile benzer etkinlikleri olduğu saptanmış olmakla beraber bir çalışmada topikal uygulamada ranibizumabın daha başarılı olduğu belirtilmiştir. 57 Etkinlik farkları muhtemelen moleküllerin büyüklükleri ve korneadan geçebilme özelliklerinden kaynaklanmaktadır.…”