title: Anti-Vascular Endothelial Growth Factor Preparations in the Treatment of Retinopathy of Prematurity: Balancing Risks and Benefits.
abstract: OBJECTIVE
  The standard of management of severe retinopathy of prematurity (ROP) is laser ablation of the peripheral retina. Intra-vitreal injection of anti- vascular endothelial growth factor antibodies has emerged as an alternative modality of treatment of ROP. The purpose of this review is to evaluate the current evidence on benefits and risks of using anti-VEGF antibodies for management of ROP.
  
  
  METHODS
  PubMed and Cochrane Register of Clinical Trials were searched for studies evaluating role of anti-VEGF agents in ROP. No study design or language restriction was used. Data were extracted using a data extraction form and presented as a summary of key findings from different study types and designs.
  
  
  RESULTS
  Of 143 studies retrieved, 107 were found relevant and further screened. Seventy-three studies reporting original research were selected. These were divided into three categories: pharmacokinetics studies (n=5), observational studies without a control group (n=59) and clinical trials with a control group (n=9). The most commonly used agent was bevacizumab at a dose of 0.625 mg per eye. At this dose bevacizumab administration led to regression of ROP in the majority of cases with type 1 ROP but was associated with sustained reduction in systemic VEGF levels. The most common adverse event after anti-VEGF therapy was recurrence of ROP needing follow up for up to one-year postmenstrual age. Randomized controlled trials demonstrated better anatomical outcome with bevacizumab as compared to laser therapy. Studies lack evidence of long term effect of bevacizumab on retinal vessels, functional visual outcomes and extra-ocular effects.
  
  
  CONCLUSIONS
  Anti-VEGF agents are effective in causing regression of ROP. However, until adequately powered studies with long term follow-up and recording of more holistic outcomes are available, anti-VEGF agents remain an investigational drug in ROP and should be used only as part of clinical study.
authors.affiliation: Departments of Pediatrics, Government Medical College Hospital, Chandigarh, India, and *University of Otago, Christchurch, New Zealand. Correspondence to: Dr Deepak Chawla, Associate Professor, Department of PediatricsGovernment Medical College Hospital, Chandigarh, India. drdeepakchawla@hotmail.com.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chawla
authors.forename: Brian A
authors.initials: BA
authors.lastname: Darlow
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D058449:Intravitreal Injections; D012178:Retinopathy of Prematurity / Q000188:drug therapy / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab