title: Risk of scar in the comparison of age-related macular degeneration treatments trials.
abstract: OBJECTIVE
  To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Prospective cohort study within a randomized clinical trial.
  
  
  METHODS
  Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).
  
  
  METHODS
  Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation.
  
  
  METHODS
  Scar formation.
  
  
  RESULTS
  Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4-3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1-1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7-3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7-3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1-2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3-2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5-0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars.
  
  
  CONCLUSIONS
  Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: ebdaniel@mail.med.upenn.edu.
authors: Ebenezer
authors: E
authors: Daniel
authors: Department of Ophthalmology, Duke University, Durham, North Carolina.
authors: Cynthia A
authors: CA
authors: Toth
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Juan E
authors: JE
authors: Grunwald
authors: Department of Ophthalmology, Duke University, Durham, North Carolina.
authors: Glenn J
authors: GJ
authors: Jaffe
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Daniel F
authors: DF
authors: Martin
authors: Department of Ophthalmology, University of Colorado-Denver, Aurora, Colorado.
authors: Stuart L
authors: SL
authors: Fine
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Jiayan
authors: J
authors: Huang
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Gui-shuang
authors: GS
authors: Ying
authors: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Stephanie A
authors: SA
authors: Hagstrom
authors: Department of Ophthalmology, Duke University, Durham, North Carolina.
authors: Katrina
authors: K
authors: Winter
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Maureen G
authors: MG
authors: Maguire
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D002921:Cicatrix / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D015994:Incidence; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011446:Prospective Studies; D000069579:Ranibizumab; D012160:Retina / Q000473:pathology*; D012307:Risk Factors; D041623:Tomography, Optical Coherence; 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: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab