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Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization: A Meta-Analysis

Papathanassiou, Miltiadis MD, PhD; Theodoropoulou, Sofia MD; Analitis, Antonis MS; Tzonou, Anastasia PhD; Theodossiadis, Panagiotis G. MD, PhD

doi: 10.1097/ICO.0b013e3182542613
Clinical Science

Purpose: To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV).

Methods: Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed.

Results: A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%–54%] overall, of 32% (95% CI, 10%–54%) for subconjunctival anti–vascular endothelial growth factor injections, and 48% (95% CI, 32%–65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by −1.71 (95% CI, −2.12 to −1.30). The subtotal pooled standardized mean differences were −1.83 (95% CI, −2.38 to −1.28) for subconjunctival anti–vascular endothelial growth factor injections and −1.50 (95% CI, −1.88 to −1.12) for topical treatment.

Conclusion: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

*2nd Department of Ophthalmology, “Attikon” University Hospital

Department of Hygiene, Epidemiology & Medical Statistics, Medical School, University of Athens, Athens, Greece.

Reprints: Miltiadis Papathanassiou, 2nd Department of Ophthalmology, “Attikon” University Hospital, 1 Rimini Strasse—124 62 Haidari, Athens, Greece (e-mail:

The authors state that they have no financial or conflicts of interest to disclose.

Received October 14, 2011

Accepted March 2, 2012

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.