title: Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  To investigate whether treatment as required 'pro re nata' (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes.
  
  
  METHODS
  Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF-inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions.
  
  
  RESULTS
  We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias.
  
  
  CONCLUSIONS
  PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD.
authors.affiliation: Cochrane Germany, Medical Center - University of Freiburg, Berliner Allee 29, 79110 Freiburg, Germany.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Schmucker
authors.affiliation: Institute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Stefan-Meier-Str. 26, 79104 Freiburg, Germany.
authors.forename: Gerta
authors.initials: G
authors.lastname: Rücker
authors.affiliation: Institute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Stefan-Meier-Str. 26, 79104 Freiburg, Germany.
authors.forename: Harriet
authors.initials: H
authors.lastname: Sommer
authors.affiliation: Department of Translational Surgery and Medicine, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Virgili
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Yoon K
authors.initials: YK
authors.lastname: Loke
authors.affiliation: Cochrane Germany, Medical Center - University of Freiburg, Berliner Allee 29, 79110 Freiburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Oeller
authors.affiliation: University Eye Center Freiburg, Killianstr. 5, 79106 Freiburg, Germany.
authors.forename: Hansjuergen
authors.initials: H
authors.lastname: Agostini
authors.affiliation: University Eye Center Freiburg, Killianstr. 5, 79106 Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ehlken
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D006801:Humans; D058449:Intravitreal Injections; D057285:Precision Medicine; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000187:drug effects; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors