title: Association of Repeated Intravitreous Bevacizumab Injections With Risk for Glaucoma Surgery.
abstract: Intravitreous injections of anti-vascular endothelial growth factor (VEGF) agents are associated with a sustained increase in intraocular pressure. This sustained elevated intraocular pressure could lead to higher rates of glaucoma surgery to lower this pressure.
  
  
  
  To determine the risk of glaucoma surgery following repeated intravitreous bevacizumab injections.
  
  
  
  This nested, case-control study acquired and analyzed data from large, population-based, linked health databases supported by the British Columbia Ministry of Health in Canada. Study participants included all patients with ophthalmic issues in British Columbia, such as those of the Provincial Retinal Diseases Treatment Program, who had received intravitreous bevacizumab injections for exudative age-related macular degeneration between January 1, 2009, and December 31, 2013. Cases were identified using glaucoma surgical codes for trabeculectomy, complicated trabeculectomy, glaucoma drainage device, and cycloablative procedure. For each case, 10 controls were identified and matched for age, preexisting glaucoma, calendar time, and follow-up time. The number of intravitreous bevacizumab injections received per year-3 or fewer, 4 to 6, or 7 or more-was determined for both cases and controls. Data analysis was performed from February 23, 2016, to November 14, 2016.
  
  
  
  Risk of glaucoma surgery compared with the number of intravitreous bevacizumab injections per year in cases and controls. Rate ratios were adjusted for covariates (diabetes mellitus, myocardial infarction, stroke, and verteporfin use).
  
  
  
  Seventy-four cases of glaucoma surgery and 740 controls were identified, with a mean (SD) age of 81.3 (8.4) years for cases and 81.4 (7.9) for controls. The case group had more males than the control group (38 [51.4%] vs 272 [36.8%]). The adjusted rate ratio of glaucoma surgery among those who received 7 or more injections per year was 2.48 (95% CI, 1.25-4.93). There was a 10.3% higher number of 7 or more injections among cases compared with controls. The adjusted rate ratio for those who received 4 to 6 injections per year compared with those who received 3 or fewer was 1.65% (95% CI, 0.84-3.23).
  
  
  
  Findings from this large, pharmacoepidemiologic study suggest that 7 or more intravitreous injections of bevacizumab annually is associated with a higher risk of glaucoma surgery and that 4 to 6 injections per year show a nonstatistically significant rate ratio in the same direction.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Brennan D
authors.initials: BD
authors.lastname: Eadie
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Etminan
authors.affiliation: Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada3Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada4Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Maberley
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Mikelberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects*; D001955:British Columbia; D016022:Case-Control Studies; D005260:Female; D005901:Glaucoma / Q000139:chemically induced / Q000601:surgery*; D020327:Glaucoma Drainage Implants; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D058449:Intravitreal Injections; D008297:Male; D017891:Pharmacoepidemiology; D019919:Prosthesis Implantation / Q000706:statistics & numerical data; D019233:Retreatment; D012307:Risk Factors; D014130:Trabeculectomy / Q000706:statistics & numerical data; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D057135:Wet Macular Degeneration / Q000188:drug therapy
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab