title: THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET.
abstract: OBJECTIVE
  Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade.
  
  
  METHODS
  Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA.
  
  
  RESULTS
  Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials.
  
  
  CONCLUSIONS
  The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets.
authors.affiliation: *Retina Vitreous Associates, Los Angeles, California; †Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria; ‡Genentech, Inc, South San Francisco, California; and §F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
authors.forename: Erin C
authors.initials: EC
authors.lastname: Henry
authors.forename: Christopher
authors.initials: C
authors.lastname: Brittain
mesh_terms: D000375:Aging; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003165:Complement System Proteins / Q000502:physiology*; D004777:Environment; D057092:Geographic Atrophy / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008268:Macular Degeneration / Q000150:complications*; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003165:Complement System Proteins