The effect of topical bevacizumab as an adjunctive therapy for corneal neovascularization

Editor, A lthough recent research on human cornea showed promising results regarding the efficacy of topical bevacizumab on corneal neovascularization (NV) (Kim et al. 2008; Dastjerdi et al. 2009), many aspects such as patient selection, long-term safety and efficacy are yet to be determined. Here, we report our experience with topical bevacizumab in the treatment of corneal NV. The records of all patients who were treated with topical bevacizumab for corneal NV between July 2007 and August 2010 were reviewed. Inclusion criterion was progressive corneal NV despite aggressive systemic and local treatment including topical corticosteroids, topical cyclosporine, autologous serum eye drops and topical vitamin A (Table 1). Bevacizumab eye drops were added to the ongoing therapy at a dose of 5 mg ⁄ml qid, as the minimal effective dose was defined as 4 mg ⁄ml previously (Habot-Wilner et al. 2010). Patients were examined at weekly intervals. Treatment with bevacizumab was terminated when no further regression of corneal NV was observed for the last 4 weeks. The extent of corneal NV was evaluated by standardized digital slit-lamp photographs (16· magnification) taken before treatment and at each visit. The neovascularized area and the total corneal area were calculated in terms of pixels by an image analysis software (imagej 1.44p, Wayne Rasband, National Institutes of Health, Bethesda, MD, USA). Neovascularization regression percentage (NRP) was calculated for pretreatment and last visit images by using the formula [(neovascularized area % before therapy-neovascularized area % after therapy) ⁄neovascularized area % before therapy] · 100. The patients were separated into two groups: group 1 (good responders) involved the first eight patients showing the highest reduction in the percentage of the vascularized area with therapy and group 2 (poor responders) involved the other eight patients on the bottom of the list, when ranked according to the regression of neovascularization. The study group consisted of 16 patients (11 men, 5 women) with corneal NV because of different aetiologies. During treatment, varying degrees of regression in the vascularized corneal area were identified in all patients and no further vessel outgrowth was observed. The mean NRP was 29.6 ± 23% overall (range, 1.8– 77.4%), 49.8 ± 15.5% (range, 35.9– 77.4%) in group 1 (good responders) and 9.4 ± 5.7% (range, 1.8 ± 17.3%) in group 2 (poor responders). The mean visual acuity (logMAR) before treatment was 0.50 ± 0.39 (range, 0.0–1.3), which significantly increased to a mean of 0.34 ± 0.19 (range, 0.0–0.7) at the end of the follow-up (p = 0.018, Wilcoxon signed-ranks test) (Table 1). The mean duration of corneal NV before the initiation of topical bevacizumab therapy was 20.2 ± 23.4 weeks (range, 1–64). The patients in the good-responders group had the corneal NV for a significantly shorter duration before treatment (8.0 ± 11.6 weeks), compared to the poor-responders group (32.4 ± 26.4 weeks) (p = 0.028, Mann–Whitney U-test) (Table 1). The mean age of the patients in the goodresponders group (29.6 ± 10.9 years) was significantly lower than the poorresponders group (47.4 ± 14.4 years) (p = 0.01,5 Mann–Whitney U-test). The duration of therapy was longer in the good-responders group who had younger neovessels; however, this difference was not statistically significant (p = 0.195, Mann–Whitney Utest) (Table 1). Ocular surface side effects were neither reported by patients nor observed during the visits. Our study showed that early treatment of actively growing vessels and lower patient age at the time of therapy showed a significantly better outcome, suggesting that the short duration of corneal NV and younger age are good prognostic indicators. Previous investigations showed increased expression of VEGF and its receptors in actively growing vessels (Bock et al. 2008). It is also known that anti-VEGF agents have an inhibitory effect on mural cell recruitment and thus vascular maturation (Greenberg & Cheresh 2009), which also explains the more potent effect of topical bevacizumab on more immature vessels, as observed in our study.