Quantifying the increasing use of anti-vascular endothelial growth factor therapy in ophthalmology

Introduction: Bevacizumab (Avastin; Genetech Inc., South San Francisco, CA) and ranibizumab (Lucentis, Genetech Inc.) are two anti-Vascular Endothelial Growth Factor (VEGF) agents used in increasing amounts off-label to treat ocular conditions. To date, no study has quantified how far reaching these therapies have been in treating eye disease and compared their off-label use to the number of clinical trials performed. Method: A systematic search of Ovid MEDLINE using the keywords bevacizumab and ranibizumab limited to “Case Reports” was used as an index of the number of diseases treated. Each keyword was also limited to “Clinical Trials, All” and “Phase III Clinical Trials” to discern the quality of evidence for these uses. Results: Bevacizumab has been utilized for the treatment of 58 different ocular conditions, but only 14 conditions were studied in a trial, and none were part of a phase III clinical trial. Ranibizumab has been used for 17 different eye conditions, with only 6 studied in a trial and only 1 disease, “wet” age-related macular degeneration reported in 4 phase III trials. In the case reports, there were 21 different adverse events ascribed to bevacizumab and 2 to ranibizumab with retinal pigment epithelial tears being the most common. Conclusion: Bevacizumab is one of the most far reaching drugs in ophthalmology and even medicine, but it is not yet supported by high quality evidence. The much higher cost of ranibizumab may be responsible for bevacizumab's popularity among eye specialists. Patients should be fully informed about the off-label use of bevacizumab and the associated risks with its use.