title: Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials.
abstract: OBJECTIVE
  To evaluate the growth of geographic atrophy (GA) during anti-vascular endothelial growth factor (VEGF) therapy.
  
  
  METHODS
  Cohort within a clinical trial.
  
  
  METHODS
  Patients included in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).
  
  
  METHODS
  Participants were randomly assigned to injections of ranibizumab or bevacizumab and to a 2-year dosing regimen of monthly or pro re nata (PRN) or to monthly for 1 year and PRN the following year. Digital color photographs and fluorescein angiograms at baseline and 1 and 2 years were evaluated for GA, and the total area of GA was measured by 2 graders masked to treatment; differences were adjudicated. Multivariate linear mixed models of the annual change in the square root of the area included baseline demographic, treatment, and ocular characteristics on imaging as candidate risk factors.
  
  
  METHODS
  Geographic atrophy growth rate.
  
  
  RESULTS
  Among 1185 participants, 86 (7.3%) had GA at baseline, 120 (10.1%) developed GA during year 1, and 36 (3.0%) developed GA during year 2. Among 194 eyes evaluable for growth, the rate was 0.43 mm/yr (standard error [SE], ±0.03 mm/year). In multivariate analysis, the growth rate was 0.37 mm/year in eyes receiving bevacizumab and 0.49 mm/year in eyes receiving ranibizumab (difference, 0.11 mm/yr; 95% confidence interval [CI], 0.01-0.22; P = 0.03). Growth rate did not differ between eyes treated monthly and PRN (P = 0.85). Eyes with subfoveal choroidal neovascularization (CNV) lesions had a lower growth rate than eyes with nonsubfoveal CNV lesions (difference, 0.12; 95% CI, 0.01-0.22; P = 0.03). Eyes with GA farther from the fovea had higher growth rates by 0.14 (95% CI, 0.01-27) mm/year for every millimeter farther from the fovea. The growth rate was 0.58 mm/year for eyes with predominantly classic lesions, 0.41 mm/year for eyes with minimally classic lesions, and 0.30 mm/year for eyes with occult only lesions (P < 0.01). The growth rate in eyes having a fellow eye with GA was higher by 0.13 mm/year (95% CI, 0.01-0.24; P = 0.03) than in eyes without GA in the fellow eye. Eyes with epiretinal membrane had a higher growth rate than eyes without epiretinal membrane (difference, 0.16; 95% CI, 0.03-0.30; P = 0.02).
  
  
  CONCLUSIONS
  Geographic atrophy growth depends on several ocular factors. Ranibizumab may accelerate GA growth.
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: juangrun@mail.med.upenn.edu.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Grunwald
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Pistilli
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Daniel
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D015331:Cohort Studies; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D057092:Geographic Atrophy / Q000235:genetics / Q000473:pathology*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D010781:Photography; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D000069579:Ranibizumab; D012697:Serine Endopeptidases / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics
chemical_list: C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D003176:Complement C3; D011506:Proteins; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D000069579:Ranibizumab